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Clinical presentation and disease associations of gout: a hospital-based study of 100 patients in Singapore

Koh WH, Seah A, Chai P

Ann Acad Med Singap, 1998 Jan;27(1):7-10.
PMID: 9588267

The aim of this retrospective study was to characterise the clinical presentation and disease associations of Oriental patients with gout seen in our hospital over a six-month period. One hundred patients comprising of 77 males and 23 females [89% Chinese, 7% Malays, 2% Indians and 2% others; mean age was 50.9 years (range 18 to 82 years), mean age at onset of disease was 43.7 years (range 16 to 78 years)] were studied. The disease was familial in 18% and 44% of patients had a history of alcohol ingestion. Co-morbid conditions included hypertension (36%), hyperlipidaemia (25%), renal failure (17%), ischaemic heart disease (13%), diabetes mellitus (4%), systemic lupus erythematosus (3%), psoriasis (2%) and ankylosing spondylitis (1%). The majority of patients (68%) had at least one associated disease. At the onset of disease, the joints commonly involved were the ankles (39%) and knees (27%) whilst the first metatarsophalangeal (MTP) joint was affected in only 26% of cases. Polyarticular onset was uncommon (n = 6). The precipitating factors reported by the patients included food (n = 23), alcohol (n = 12), drugs (n = 4), trauma (n = 3) and surgery (n = 2). Eleven patients had a history of renal calculi and 15% had tophaceous gout. Majority of patients (71%) had been treated with urate-lowering drugs (allopurinol). We concluded that gout in Singapore predominantly affects middle-aged men who often have an accompanying illness.

Matched MeSH terms: Risk Factors
Ankylosing spondylitis in Singapore: a study of 150 patients and a local update

Koh WH, Boey ML

Ann Acad Med Singap, 1998 Jan;27(1):3-6.
PMID: 9588266

This paper presents the results of a clinical study of 150 patients in Singapore with ankylosing spondylitis (AS) and reviews recent developments locally with regards to the disease. The patients were predominantly males (ratio 7:1) and Chinese (n = 147). The onset of disease is usually in the early twenties and there was a mean delay of 6.3 years before diagnosis was made. Peripheral joint involvement is common but apart from uveitis (17%), extra-articular manifestations are rare. AS patients have abnormal lipid profiles and lower bone mineral density compared to healthy controls. HLA*B2704 is the predominant subtype in our Chinese patients whilst HLA*B2706 was found only in healthy controls. Intensive group physiotherapy is beneficial for patients with spondyloarthropathy.

Matched MeSH terms: Risk Factors
Psychiatric morbidity in the first-degree relatives of schizophrenic patients

Varma SL, Zain AM, Singh S

Am. J. Med. Genet., 1997 Feb 21;74(1):7-11.
PMID: 9033998

There is increasing evidence that genetic factors play a role in the etiology of schizophrenic disorders. One thousand eighty-nine first-degree relatives of schizophrenics and 1,137 controls were studied to discover their psychiatric morbidity. Psychiatric morbidity was found in 16.34% of the first-degree relatives (FDR) of schizophrenics (parents, 5.69%; siblings, 7.71%; offspring, 2.94%) as compared to 6.9% in the controls (P < 0.001). Schizophrenia was found in 8.3% of the patient group, which was significantly higher (0.2%) as compared to the controls. Schizoid-schizotypal personality disorder was found in 3.03% of FDRs of the schizophrenic group. Depressive disorder was found in 4.4% and 2.1% in the control and patient group, respectively, which was statistically significant. Morbidity risk of schizophrenia was found in 16.97%, 6.22% and 5.79% of schizophrenia, schizoid-schizotypal personality disorder and depressive disorder, respectively, in the FDR of schizophrenic group.

Matched MeSH terms: Risk Factors
Comparison of morbidities in very low birthweight and normal birthweight infants during the first year of life in a developing country

Boo NY, Ong LC, Lye MS, Chandran V, Teoh SL, Zamratol S, et al.

J Paediatr Child Health, 1996 Oct;32(5):439-44.
PMID: 8933407

OBJECTIVE: To compare the morbidities in the very low birthweight (VLBW; < 1500 g) and normal birthweight (NBW; > or = 2500 g) Malaysian infants during the first year of life.
METHODOLOGY: Prospective observational cohort study of consecutive surviving VLBW infants and randomly sampled NBW infants born in the Kuala Lumpur Maternity Hospital between 1 December 1989 and 31 December 1992. Infants were followed up regularly during the first year of life, after correction for prematurity.
RESULTS: Compared with NBW infants (n = 106), VLBW infants (n = 127) had significantly higher risk of failure to thrive (odds ratio [OR] = 8.0, 95% confidence intervals [CI]: 1.1 to 354.3), wheezing (OR = 3.7, 95% CI: 1.6 to 9.3), rehospitalization (OR = 2.3, 95% CI: 1.1 to 5.0), cerebral palsy (OR = 8.6, 95% CI: 2.0 to 77.6), neurosensory hearing loss (OR = 12.0, 95% CI: 1.7 to 513.6) and visual loss (7.9 vs 0%, P = 0.002). The mean mental developmental index (MDI) and mean psychomotor developmental index (PDI) at 1 year of age were significantly lower among VLBW infants (MDI 99 [SD = 28], PDI 89 [SD = 25]) than NBW infants (MDI 106 [SD = 18], PDI 101 [SD = 18]) (95% CI for difference between means being MDI: -14.1 to -1.7; and PDI: -17.6 to -6.0). Logistic regression analysis showed that among VLBW infants: (i) male sex, Malay ethnicity and bronchopulmonary dysplasia were significant risk factors associated with wheezing; (ii) longer duration of oxygen therapy during the neonatal period, seizures after the post-neonatal period and wheezing were significant risk factors associated with rehospitalization; and (iii) longer duration of oxygen therapy during the neonatal period was a significant risk factor associated with adverse neurodevelopmental outcome during the first year of life.
CONCLUSIONS: Compared with NBW infants, VLBW Malaysian infants had significantly higher risks of physical and neuro-developmental morbidities.

Matched MeSH terms: Risk Factors
Child sexual abuse: psychosocial aspects of 101 cases seen in an urban Malaysian setting

Kassim K, Kasim MS

Child Abuse Negl, 1995 Jul;19(7):793-9.
PMID: 7583735

This paper describes a case note and interview study of a cross sectional sample comprised of all children seen and confirmed as being sexually abused between June 1985 and December 1990 by the Suspected Child Abuse and Neglect (SCAN) Team of Kuala Lumpur General Hospital. A total of 101 cases, which represented 18.2% of all child abuse cases, were seen together with their accompanying adults. Information about ethnicity, socioeconomic status, family constellation relationship of perpetrator to the child, and reported psychosocial factors that could have contributed towards the abuse were recorded. The Indian ethnicity group was found to be overrepresented. The mean age of children was 6-8 years, SD 4.1, with age ranging 1.5-16 years. Forty-one and one-half percent were in the age range 5-9 years. Among the important associated psychosocial factors found were the absence of another adult at home, unemployment, and history of drug abuse among the perpetrators.

Matched MeSH terms: Risk Factors
Patterns of risk behaviour for patients with sexually transmitted diseases and surveillance for human immunodeficiency virus in Kuala Lumpur, Malaysia

Lye MS, Archibald C, Ghazali AA, Low BT, Teoh BH, Sinniah M, et al.

Int J STD AIDS, 1994 Mar-Apr;5(2):124-9.
PMID: 8031914 DOI: 10.1177/095646249400500209

A study was conducted to determine the feasibility of establishing a sentinel human immunodeficiency virus (HIV) surveillance system involving patients with sexually transmitted diseases attending private clinics and a government sexually transmitted disease clinic in Kuala Lumpur, Malaysia. Information on risk behaviours for HIV infection were also collected. A total of 84 female and 91 male patients were interviewed and tested for HIV infection; 41.7% of the women reported working as prostitutes, other occupations included masseuses, hairdressers, waitresses, salesgirls, receptionists, factory workers, and others. The most common diagnosis was gonorrhoea. Other diagnoses included non-specific genital infection, pelvic inflammatory disease, genital herpes and syphilis. 58.3% of the women had a hundred or more sex partners during the previous month; 99% had 6 or more sex partners. Only 4.8% of female patients had their male partners using condoms most of the time, 11.9% hardly used condoms at all. Of the males, 93.3% were heterosexual, while 6.7% were bisexuals, 41.1% had between 6-20 different partners in the previous year. 78.0% of them had prostitutes as their sex partners most of the time. 41.8% had experiences in Thailand and the Philippines. 73.6% never used condoms, while 19.8% only used condoms rarely. Although all patients were tested negative for HIV antibodies, lot quality assurance sampling methods indicate that the upper limits of prevalences for females and males were 3.5% and 3.3% respectively, at a 5% type I error. The study has shown that it is feasible to carry out a sentinel surveillance programme among STD patients and provided useful baseline data for future comparisons.(ABSTRACT TRUNCATED AT 250 WORDS)

Matched MeSH terms: Risk Factors
Ultrasound screening of the abdominal aorta in Malaysians

Teoh MK, Ramasamy D, Wong KP

Aust N Z J Surg, 1992 Nov;62(11):862-5.
PMID: 20169704

Ultrasound examination of the abdominal aorta was performed on 100 patients with cardiovascular disease and a control group of 100 subjects. The objectives were to define the normal aortic size of Malaysians, to screen for aneurysms and to compare the aorta size of the different population groups. In the study group the mean anteroposterior (AP) diameter of the non-aneurysmal aortas at the level of the renal arteries was 1.82 cm (range 0.9-2.6 cm) in men and 1.83 cm (range 1.5-2.3 cm) in women. This compares with 1.61 cm (range 1.1-2.2 cm) in men and 1.50 cm (range 0.8-2.4 cm) in women in the control group. The dimensions of the infrarenal aorta show a similar relationship between the two groups. These AP diameters were significantly smaller than the published figures from studies done on Western populations and are consistent with the smaller stature of Malaysians. Five aneurysms and one ectasia were found (mean size 5 cm, range 3.5-6.0 cm), all in men aged 50-75 years in the study group, and none in the control group. All the aneurysms were easily palpable in these patients who were thinner than the average Caucasian. Given the lower incidence of aortic aneurysms in Malaysians there is no role for routine ultrasound screening of the population. High risk groups can be adequately screened by clinical examination alone.

Matched MeSH terms: Risk Factors
Do dysplastic and adenomatous changes in large bowel hamartomas predispose to malignancy?--A report of two cases

Visvanathan R, Thambidorai CR, Myint H

Ann Acad Med Singap, 1992 Nov;21(6):830-2.
PMID: 1338270

Two patients, members of one family, with Peutz-Jeghers syndrome are described who underwent surgery for bowel obstruction. Both had multiple polyps in the gastrointestinal tract. Severe dysplasia and adenomatous change were present in two hamartomatous polyps adjacent to a stenosing colonic carcinoma in one patient and moderate dysplasia and adenomatous change were observed in two hamartomatous rectal polyps in his son. These changes support recent reports in the literature of progression towards neoplasia in these lesions.

Matched MeSH terms: Risk Factors
Non-typhoid Salmonella gastroenteritis

Lee WS, Puthucheary SD, Boey CC

J Paediatr Child Health, 1998 Aug;34(4):387-90.
PMID: 9727185

OBJECTIVE: To study the clinical features of non-typhoid Salmonella gastroenteritis and the incidence, risk factors and outcome of invasive complications in urban Malaysian children. To describe the serotypes of Salmonella species isolated and the pattern of antibiotic susceptibility.
METHODOLOGY: Retrospective review of a group of 131 children with non-typhoid Salmonella gastroenteritis seen at the University Hospital, Kuala Lumpur, Malaysia from January 1994 to December 1996.
RESULTS: Sixty-seven percent were infants below one year of age. Fever and vomiting were seen in nearly half of children. Seven children (5.3%) had invasive complications: 5 bacteraemia and 2 meningitis. Age below 6 months, fever > 38.0 degrees C, and dehydration on admission were significantly associated with invasive complications. The commonest serotypes isolated were S. enteritidis, S. paratyphi B, and S. bovis-morbificans. A total of 94-100% of isolates were susceptible to commonly prescribed antibiotics.
CONCLUSIONS: Children with Salmonella gastroenteritis below 6 months of age who are febrile and dehydrated should be treated empirically with antibiotics until the result of blood culture is available.

Matched MeSH terms: Risk Factors
Social factors in relation to physical abuse in Kuala Lumpur, Malaysia

Kasim MS, Shafie HM, Cheah I

Child Abuse Negl, 1994 May;18(5):401-7.
PMID: 8032970

Available evidence has shown that the type of abuse perpetrated on children depends considerably on the social and other factors inherently faced by these children. A total of 119 cases of physical abuse was detected by the Suspected Child Abuse and Neglect (SCAN) Team of General Hospital, Kuala Lumpur in 1991. Eighty-two cases were categorized as mild and 37 as severe. The average age of those mildly abused was 7.9 years, for those severely abused the average age was 4.2 years. The perpetrators of those mildly abused were often their own parents. However, among those severely abused, the child-minder was the most frequent abuser. Ninety-two of all cases were in families of social classes IV and V. In 47 cases, there was definite evidence of family disharmony or disruption. Among the 37 severely abused, the parents were either divorced or separated in 14 cases. There was a personality disorder in seven of the cases. Six of the abusers were also using drugs and nine were alcoholics. This paper shows that, even in a developing country, the social milieu is important in the type of abuse inflicted.

Matched MeSH terms: Risk Factors
Prevalence and determinants of cervical cancer screening: a community-based study in Singapore

Seow A, Lee HP

Ann Acad Med Singap, 1994 May;23(3):342-7.
PMID: 7944247

A cross-sectional survey of 568 married women aged 21-65 years in the Pasir Panjang Constituency was conducted to determine the prevalence of cervical cancer screening in the community and the factors affecting acceptance of this screening test. Results show that 309 (54.4%) of the respondents had ever had a Pap smear. The women who reported having had a smear were more likely to be below 45 years of age (prevalence ratio 1.47, 95% confidence interval 1.15 to 1.88), Chinese and of a higher socioeconomic status (1.68, 1.33 to 2.12). They were also more likely to have married at a later age (1.68, 1.21 to 2.31) than women who had not had a smear. Age and socioeconomic status remained independent predictors on multivariate analysis. The findings suggest that an important task of public health practitioners is to increase the uptake of screening among older and socially disadvantaged women who are known to be at the highest risk of cervical cancer. In addition, strategies to encourage younger women to continue regular attendance at screening clinics beyond their childbearing years will be important for the future.

Matched MeSH terms: Risk Factors
Epidemiology of cervical carcinoma in Brunei Darussalam. Analysis of data on 27,208 women screened with cytologic examinations

Affandi MZ, Dun T, Mantuano V, Sidhu R, Lumplugh C, Telisinghe PU

Acta Cytol., 1993 Mar-Apr;37(2):175-80.
PMID: 8465637

During the five-year period from January 1985 to December 1989 a total of 27,208 women, representing 44.0% of the total female population over age 15 years in Brunei Darussalam, underwent a cytologic examination. The majority of them were Malays (62.32%), followed by Chinese (22.23%), while the remainder were the expatriate population living in the country. High grade squamous intraepithelial lesion (moderate dysplasia) was detected in 88 women (3.3/1,000), high grade squamous intraepithelial lesion (carcinoma in situ) was seen in 32 women (1.22/1,000), and invasive carcinoma was found in 43 women (1.37/1,000). The overall detection rate for cervical cancer was 2.79/1,000 women in the population screened. In Brunei Darussalam Malay women marry at an early age, 44% by the age of 19 years, leading to sexual contact before the age of 20. However, the incidence of cervical cancer is low among them. This could be because they belong to the Orthodox Muslim Society, in which promiscuity is not permitted. Hence, multiple sex partners could be an important factor in the etiology of cervical cancer, confirming the current trend of thought that cervical cancer is a sexually transmitted disease. A comparison of the epidemiologic risk factors among the various races living in Brunei Darussalam is made.

Matched MeSH terms: Risk Factors
Mitomycin C adjuvant chemotherapy after Wertheim's hysterectomy for stage IB cervical cancer

Sivanesaratnam V, Jayalakshmi P

Cancer, 1989 Aug 15;64(4):798-800.
PMID: 2501019

Patients undergoing radical surgical treatment for Stage IB and IIA cervical carcinoma are at high risk of developing local recurrence and/or distant metastases when one or more of the following factors are present: presence of metastatic pelvic lymph nodes, a large primary growth, full-thickness tumor invasion of the cervix, clinically undetected parametrial extension, and lymphatic/vascular channel permeation in the cervix by tumor cells. Carcinoma of the cervix appears to be behaving like a systemic disease. Therefore, systemic measures should be considered in its therapy. The authors report the initial experience with the use of mitomycin C as a single agent adjuvant in 16 patients with Stage IB carcinoma of the cervix who had undergone Wertheim radical hysterectomy and were thought to be in this high-risk group. Fourteen of the patients are alive and free of disease after durations of follow-up ranging from 16 to 38 months, the disease-free survival at a median follow-up of 29 months being 87.5%. One patient required discontinuation of adjuvant chemotherapy because of severe marrow toxicity; however, in view of the presence of a multiple risk factors, pelvic irradiation was given instead. She died 13 months later from disseminated disease. A second patient died 6 months later from congestive cardiac failure.

Matched MeSH terms: Risk Factors
Methicillin-resistant Staphylococcus aureus in surgical patients: Malaysian experience

Lee SH, Yii NW, Hanifah YA

J R Coll Surg Edinb, 1991 Oct;36(5):323-7.
PMID: 1757914

Methicillin-resistant Staphylococcus aureus has emerged as an important cause of nosocomial infections in recent years. During 1988 in the Department of Surgery of the University Hospital in Kuala Lumpur, Malaysia, 148 patients were shown to be infected or colonized with these organisms. The patients at risk were those who stay in hospital for greater than 14 days, those over 50 years of age, patients who underwent neurosurgery, cardiothoracic surgery, or were admitted with major burns. Of the 148 patients, 78 (52.7%) were clinically infected, the remaining 70 being colonized. A total of 28 patients died (18.9%) but only five (3.4%) as a direct result of this infection. The estimated annual cost of controlling the organism was found to be approximately MR$250,000. (50,000 pounds). This nosocomial infection therefore represents a serious problem, especially in developing countries where health funding and health facilities are limited.

Matched MeSH terms: Risk Factors
Fulltext Disease impact and patient insight--a study on a local population of asthmatics

Ahmad NS, Chan MY, Hiew FL, Sharif SA, Vijayasingham P, Thayaparan T, et al.

Med J Malaysia, 2003 Oct;58(4):526-32.
PMID: 15190628

The cornerstone of asthma management is achieving adequate symptom control and patient education. We studied in our local population of asthmatic patients how well their symptoms were controlled with currently prescribed treatment and their insight into the disease and its management. Over a 6-month period, 93 asthmatics recruited from two local government health clinics and a state hospital were interviewed using a standard questionnaire. Patients were classified into 4 groups based on the treatment they were on according to Global Initiative for Asthma (GINA) treatment guidelines. The number of patients in Step 1 (rescue medication alone), Step 2 (1 controller medication), Step 3 (2 controller medications) and Step 4 (at least 3 controller medications) were 8, 39, 34 and 12, respectively. Except for day symptoms in Step 1 group, fewer than 50% achieved minimum day or night symptoms and no restriction of daily activities. Questions on patient insight were only available for 50 patients. Weather change (74%), air pollution (66%) and physical stress (46%) were the three highest ranked common asthma triggers. More than half correctly recognized the important symptoms of a serious asthma attack but fewer than 15% were familiar with the peak flow meter and its use or with the asthma self-management plan. Most patients perceived that their treatment had helped reduce disease severity and exacerbations. We conclude that symptom control and some aspect of patient education are still lacking in our local asthmatics.
Study site: Hospital Tuanku Jaafar, Seremban, Negeri Sembilan; Klinik Kesihatan Seremban; Klinik Kesihatan Ampangan, Malaysia

Matched MeSH terms: Risk Factors
Toxoplasmosis: prevalence and risk factors

Nissapatorn V, Noor Azmi MA, Cho SM, Fong MY, Init I, Rohela M, et al.

J Obstet Gynaecol, 2003 Nov;23(6):618-24.
PMID: 14617462

A total of 200 pregnant women were recruited in this cross-sectional study. The overall seroprevalence of toxoplasmosis in pregnant women was found to be 49%, in which 39%, 4% and 6% for anti-Toxoplasma IgG, IgM and both anti-Toxoplasma IgG and IgM antibodies, respectively. We found the differences in Toxoplasma seroprevalence rates among the races were significant: the highest rate was in the Malays (55.7%), followed by the Indian (55.3%) and the Chinese (19.4%) (P<0.05) populations. An increase in Toxoplasma seroprevalence with increasing parity was detected (P<0.05). Women with no children had a prevalence of 39.7%, while women with one or more than two children had a prevalence of 44.2% and 62.9%, respectively. In this study, there was no significant association between Toxoplasma seroprevalence and various possible risk factors in pregnant women (P>0.05). When multivariate analysis was performed, no significant association between Toxoplasma seroprevalence and history of contact with cats, consumption of undercooked meat and blood transfusion was found (P>0.05). We did not find any newly diagnosed cases of acute acquired toxoplasmosis in pregnancy during the study period.

Matched MeSH terms: Risk Factors
Management of gestational trophoblastic disease in developing countries

Sivanesaratnam V

Best Pract Res Clin Obstet Gynaecol, 2003 Dec;17(6):925-42.
PMID: 14614890 DOI: 10.1016/S1521-6934(03)00097-X

In Malaysia, the incidence of molar pregnancy and gestational trophoblastic neoplasia is 2.8 and 1.59 per 1000 deliveries, respectively; the disease is more common among the Chinese compared to the Malays and Indians. While uterine suction is the preferred method of uterine evacuation of hydatidiform mole, complete evacuation was not achieved at the first attempt in 25% of cases. Partial moles comprise 30% of all moles; these need follow up similar to that for complete moles as they are potentially malignant. In the management of invasive moles, chemotherapy should not be withheld in the presence of metastases or failure of regression of hCG. Placental site tumours are rare. Prophylactic hysterectomy and prophylactic chemotherapy are not recommended. However, in those patients with unsatisfactory hCG regression curves indicating 'at risk' in developing gestational trophoblastic neoplasia (GTN), 'selective preventive chemotherapy' appears appropriate. Chemotherapy remains the main modality of treatment for GTN. As tumour bulk and location of disease are important determinants in outcome, we categorized our patients into low, medium- and high-risk groups with survivals of 100, 98 and 61.7% respectively. Surgery and radiotherapy have a limited role.

Matched MeSH terms: Risk Factors
Fulltext Prevalence of and risk factors for anal high-risk HPV among HIV-negative and HIV-positive MSM and transgender women in three countries at South-East Asia

Somia IKA, Teeratakulpisarn N, Jeo WS, Yee IA, Pankam T, Nonenoy S, et al.

Medicine (Baltimore), 2018 Mar;97(10):e9898.
PMID: 29517698 DOI: 10.1097/MD.0000000000009898

This study aimed to assess the prevalence of and associated risk factors for anal high-risk human papillomavirus (hr-HPV) infection among men who have sex with men (MSM) and transgender women (TGW) in Indonesia, Thailand, and Malaysia.This was baseline data from a prospective cohort study with clinic sites in Jakarta and Bali (Indonesia), Bangkok (Thailand), and Kuala Lumpur (Malaysia).MSM and TGW aged 18 years and older from Indonesia, Thailand, and Malaysia were enrolled. Demographic and behavioral characteristics were assessed, and anal samples were collected for HPV genotyping. Multivariate logistic regression models were used to assess risk factors for anal hr-HPV overall and among HIV-positive participants.A total of 392 participants were enrolled, and 48 were TGW. As many as 245 were HIV-positive, and 78.0% of the participants were on combination antiretroviral therapy (cART). Median CD4 count was 439 cells/mm and 68.2% had undetectable HIV-RNA. HIV-positive participants had significantly more hr-HPV compared to HIV-negative participants (76.6% vs 53.5%, P risk type (20%), whereas HPV-33, -39, and -58 were significantly more common among HIV-positive participants. HIV-positive participant significantly associated with anal hr-HPV infection compared with HIV-negative (OR: 2.87, 95% CI: 1.76-4.70, P ≤ .001), whereas among HIV-positive participants transgender identity had lower prevalence of hr-HPV infection (OR: 0.42, 95% CI: 0.19-0.91, P = .03).High-risk HPV infection was very common among MSM and TGW in South-East Asia. Overall, HIV-infection, regardless of cART use and immune status, significantly increased the risk, while among HIV-positive participants transgender identity seemed to decrease the risk of anal hr-HPV.

Matched MeSH terms: Risk Factors
Fulltext Ion channels, long QT syndrome and arrhythmogenesis in ageing

Jeevaratnam K, Chadda KR, Salvage SC, Valli H, Ahmad S, Grace AA, et al.

Clin Exp Pharmacol Physiol, 2017 12;44 Suppl 1:38-45.
PMID: 28024120 DOI: 10.1111/1440-1681.12721

Ageing is associated with increased prevalences of both atrial and ventricular arrhythmias, reflecting disruption of the normal sequence of ion channel activation and inactivation generating the propagated cardiac action potential. Experimental models with specific ion channel genetic modifications have helped clarify the interacting functional roles of ion channels and how their dysregulation contributes to arrhythmogenic processes at the cellular and systems level. They have also investigated interactions between these ion channel abnormalities and age-related processes in producing arrhythmic tendency. Previous reviews have explored the relationships between age and loss-of-function Nav 1.5 mutations in producing arrhythmogenicity. The present review now explores complementary relationships arising from gain-of-function Nav 1.5 mutations associated with long QT3 (LQTS3). LQTS3 patients show increased risks of life-threatening ventricular arrhythmias, particularly after 40 years of age, consistent with such interactions between the ion channel abnormailities and ageing. In turn clinical evidence suggests that ageing is accompanied by structural, particularly fibrotic, as well as electrophysiological change. These abnormalities may result from biochemical changes producing low-grade inflammation resulting from increased production of reactive oxygen species and superoxide. Experimental studies offer further insights into the underlying mechanisms underlying these phenotypes. Thus, studies in genetically modified murine models for LQTS implicated action potential recovery processes in arrhythmogenesis resulting from functional ion channel abnormalities. In addition, ageing wild type (WT) murine models demonstrated both ion channel alterations and fibrotic changes with ageing. Murine models then suggested evidence for interactions between ageing and ion channel mutations and provided insights into potential arrhythmic mechanisms inviting future exploration.

Matched MeSH terms: Risk Factors
Fulltext Age-dependent atrial arrhythmic phenotype secondary to mitochondrial dysfunction in Pgc-1β deficient murine hearts

Valli H, Ahmad S, Chadda KR, Al-Hadithi ABAK, Grace AA, Jeevaratnam K, et al.

Mech Ageing Dev, 2017 Oct;167:30-45.
PMID: 28919427 DOI: 10.1016/j.mad.2017.09.002

INTRODUCTION: Ageing and several age-related chronic conditions including obesity, insulin resistance and hypertension are associated with mitochondrial dysfunction and represent independent risk factors for atrial fibrillation (AF).
MATERIALS AND METHODS: Atrial arrhythmogenesis was investigated in Langendorff-perfused young (3-4 month) and aged (>12 month), wild type (WT) and peroxisome proliferator activated receptor-γ coactivator-1β deficient (Pgc-1β-/-) murine hearts modeling age-dependent chronic mitochondrial dysfunction during regular pacing and programmed electrical stimulation (PES).
RESULTS AND DISCUSSION: The Pgc-1β-/- genotype was associated with a pro-arrhythmic phenotype progressing with age. Young and aged Pgc-1β-/- hearts showed compromised maximum action potential (AP) depolarization rates, (dV/dt)max, prolonged AP latencies reflecting slowed action potential (AP) conduction, similar effective refractory periods and baseline action potential durations (APD90) but shortened APD90 in APs in response to extrasystolic stimuli at short stimulation intervals. Electrical properties of APs triggering arrhythmia were similar in WT and Pgc-1β-/- hearts. Pgc-1β-/- hearts showed accelerated age-dependent fibrotic change relative to WT, with young Pgc-1β-/- hearts displaying similar fibrotic change as aged WT, and aged Pgc-1β-/- hearts the greatest fibrotic change. Mitochondrial deficits thus result in an arrhythmic substrate, through slowed AP conduction and altered repolarisation characteristics, arising from alterations in electrophysiological properties and accelerated structural change.

Matched MeSH terms: Risk Factors

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