Phenotyping and Genotyping of HNA: Prevalence,Risk of Alloimmunization,and HNA Incompatibilities in Indians

BackgroundAntibodies to human neutrophil alloantigens (HNA) are involved in the pathophysiology of several clinical conditions including transfusion-related acute lung injury (TRALI), alloimmune and autoimmune neutropenia, and febrile nonhemolytic transfusion reactions leading to neutropenia. The cognate antigens are polymorphic structures expressed on several glycoproteins on the neutrophils, i.e., antigens HNA-1a, −1b, −1c, and −1d on Fc-γ-receptor IIIb; HNA-2 on CD177; HNA-3a and −3b on choline transporter-like protein 2; HNA-4a and −4b on CD11b/αM subunit of the αMβ2-integrin (CD11b/CD18, Mac-1, CR3); and HNA-5a and −5b on αL-subunit (CD11a) of the αLβ2 integrin (CD11a/CD18), leukocyte function associated molecule (LFA)-1. Currently, there is a lacuna of diagnostic methods for detection of HNA in India. This study aimed to determine the HNA frequencies in Indians, estimate the risk of alloimmunization, and prepare typed neutrophil panels, which can be used to detect HNA antibodies in neutropenia cases.Material and MethodsEDTA blood samples were collected from random 1,054 blood donors. HNA-2 was phenotyped on fresh EDTA samples using FITC labelled monoclonal anti-CD177 by flowcytometry. HNA-1 (FCGR3B) genotyping was carried out by DNA sequencing and PCR-RFLP. Antigens of HNA-3 (SLC44A2) and HNA-5 (ITGAL) were genotyped by PCR-RFLP using TaqαI and Bsp1286I restriction enzymes, respectively, while HNA-4 (ITGAM) was genotyped by PCR-SSP.ResultsAllele frequencies of FCGR3B*01, FCGR3B*02, and FCGR3B*03 were found to be 0.433, 0.444, and 0.087, respectively. FCGR3B*01+*02+*03− was the most common genotype (33.78%). Ten individuals showed deficiency of FCGR3B individuals, while 23 showed hyperexpression, i.e., FCGR3B*01+*02+*03+. FCGR3B*04and *05 occurred with a frequency of 0.002 and 0.024. HNA-2 was found to be a high frequency antigen occurring in 98.8% population. Four percent individuals showed atypical expression of CD177 on their neutrophils. Allele frequencies of SLC44A2*01 and SLC44A2*02were 0.812 and 0.188, respectively, and that of ITGAM*01, ITGAM*02, ITGAL*01, and ITGAL*02 were 0.9546, 0.0454, 0.2372, and 0.7628, respectively.ConclusionThis is the first study in India to report the frequencies of HNA among blood donors. Typed neutrophil panels identified in the present study will enable us to investigate suspected cases of immune neutropenia in future.Key Words: Human neutrophil antigen alloimmunization, Human neutrophil alloantigens, Indians, Neutropenia, Transfusion-related acute lung injury     

Molecular characterization showed limited genetic diversity among Salmonella Enteritidis isolated from humans and animals in Malaysia

Salmonella enterica serovar Enteritidis (S. Enteritidis) is the most common causative agent of non-typhoidal salmonellosis in Malaysia. We aimed to characterize S. Enteritidis isolated from humans and animals by analyzing their antimicrobial resistance profiles and genotypes. A total of 111 strains were characterized using multiple-locus variable-number tandem repeat analysis, pulsed-field gel electrophoresis, and antimicrobial susceptibility testing. Both typing methods revealed that genetically similar S. Enteritidis strains had persisted among human and animal populations within the period of study (2003–2008). Only 39% of the strains were multi-drug resistant (i.e., resistant to 3 or more classes of antimicrobial agents), with a majority (73%) of these in low-risk phase (multiple antibiotic resistant index <0.20). Limited genetic diversity among clinical and zoonotic S. Enteritidis suggested that animals are possible sources of human salmonellosis. The degree of multi-drug resistance among the strains was generally low during the study period.     

潍坊地区无偿献血者HLA抗体和HNA抗体检测情况分析

目的:通过随机抽样检测潍坊地区无偿献血者血清HLA抗体及HNA抗体阳性率,评估在潍坊献血人群中开展HLA及HNA抗体筛查的必要性.方法:随机选取有输血、妊娠、移植等免疫史的无偿献血者208例作为实验组,选取无上述免疫史的无偿献血者168例作为对照组,运用流式荧光微珠法对两组标本进行HLA抗体和HNA抗体检测,运用统计分...     

Microbiological aetiology of acute dacryocystitis in hospital Universiti Sains Malaysia,Kelantan Malaysia

ObjectiveTo determine the microbiological aetiology of acute dacryocystitis presented to the Hospital University Sains Malaysia, Kubang Kerian, Kelantan in 5 years duration from 2005 until 2010.MethodsThis is a retrospective analysis of patients who were clinically diagnosed as acute dacryocystitis from 2005 until 2010 to determine the regional microbiological pattern. The age, gender, predisposing factors, intravenous antibiotics and their microbiological results of discharge from punctal expression were collected. The laboratory procedures were in accordance with the Clinical and Laboratory Standards Institute guidelines.ResultsThere were 23 patients admitted to the eye ward during study period. Females (n=17) outnumbered males (n=6). Majority of isolates were Gram-positive bacteria (n=10, 43.4%) followed by Gram-negative isolates (n=2, 12.9%). The most predominant isolates were Streptococcus pneumonia (S. pneumonia) (21.7%) followed by Staphylococcus epidermidis (S. epidermidis) (13.0%).ConclusionsS. pneumoniae was the commonest gram positive organism identified in our study. 47.8% patients showed resistant to initial empirical treatment.     

The burden of terrorism in Malaysia

In the peace-loving, moderate and progressive country of Muslim-dominated Malaysia, violence generally is alien to the culture. Terrorism initially took shape during the post-independence, communist era by jungle recalcitrant actions. In recent years, this has been superceded by a more internationally related trend of violence. Only very few incidents were based locally, while the majority were linked to international groups or organizations abroad, including the Kumpulan Mujahidin Malaysia (KMM), Jemaah Islamiyah (JI), and the Abu Sayyaf Group (ASG). Kidnapping with ransom seemed to have been the most commone modus operandi, while killing and robbery accounted for very few of these incidents. The number of victims in each event so far has been small, and smaller for those physically harmed or killed. This pattern of terrorist attacks suggests that the current level of provision of emergency medical services is sufficient to handle such incidents. Recent advances in local emergency medicine also have witnessed the establishment of various teaching and training modules, a pivotal role played by university hospitals and supported by the Ministry of Health. However, the spate of ongoing events of mass destruction such as the conflict in Israel/Palestine, wars in Afghanistan and Iraq, the World Trade Center and Pentagon tragedies of 11 September 2001, and the Bali bombing in Indonesia, remain as great concerns to Malaysians. Both the government and the people of Malaysia abhor such unjustified uses of terror, and take every measure to curtail them. The National Security Council policies of Arahan No. 18 and Arahan No. 20 detail specific roles and responsibilities of various agencies in managing terrorism and disasters respectively, while the use of the stern Internal Security Act that allows indefinite detention without trial, evidently has been an efficient intelligence and security apparatus. With more recent developments of terrorist events regionally and globally, Malaysia continues to face an ongoing threat from such activities. Various measures have been and will be actively undertaken both by government and non-governmental agencies in facing these challenges.     

Prevalence and outcome of peripartum cardiomyopathy in Malaysia

Introduction: Peripartum cardiomyopathy (PPCM) is an uncommon form of congestive heart failure, afflicting obstetric patients around the time of delivery. The epidemiology of PPCM is infrequently reported. To the best of our knowledge, there has been no report from Asia. Objective: To define the prevalence, presentation and outcome of PPCM in a major referral centre in Malaysia. Methodology: Retrospective case record analysis of all patients admitted and diagnosed with PPCM at the University Malaya Medical Centre, Kuala Lumpur, over 5 years from 1st January, 2001 to 31st December, 2004. Results: Eight patients were diagnosed with PPCM over the study period reflecting a prevalence of 34: 100,000 life births. Five were diagnosed within 5 months after delivery. Three were associated with twin pregnancies. There was one death (12.5% mortality). The mean left ventricular ejection fraction (LVEF) at the time of diagnosis was 27.1 ± SD 6.4% (range: 17–35%). Following the index event, the left ventricular function recovered in three of the eight patients (37.5%) with restoration of normal LVEF (LVEF > 50%). Two patients had subsequent pregnancies. One was terminated at 7 weeks, and the other delivered uneventfully with a normal LVEF. Conclusions: Peripartum cardiomyopathy is uncommon in Malaysia. It appears to be associated with twin pregnancy. The outcome is variable with 37.5% recovering normal left ventricular function, 12.5% mortality and persistently impaired left ventricular function in the remainder.     

Benefit of outpatient cardiac rehabilitation in under-represented patient subgroups.

OBJECTIVE: To assess the effect of outpatient cardiac rehabilitation in important patient subgroups. DESIGN: Prospective cohort study. SUBJECTS: Consecutive patients from March 1999 until July 2003. METHODS: This study assessed the results of symptom-limited bicycle stress testing and health-related quality of life (Profil der Lebensqualit?t Chronisch Kranker) at baseline and after a 3-month rehabilitation program, and complications and drop-outs during outpatient cardiac rehabilitation. RESULTS: Of 1061 patients, 155 (15%) women, 87 (8%) men aged >or= 75 years, 162 (15%) had diabetes mellitus and 88 (8%) did not speak the local language. Reasons for outpatient cardiac rehabilitation included acute coronary artery disease (87%), valvular heart disease (9%) and congestive heart failure (1%). Mean age was 62 years (standard deviation 11). Patients increased both their age- and body-weight-adjusted workload (p < 0.0001) and quality of life (p < 0.0001) during the program. Although the initial workload achieved was lower than for normal patients (p < 0.0001), it increased in all subgroups during outpatient cardiac rehabilitation (p < 0.0001). Baseline quality of life was lower in women, but increased in most dimensions for all subgroups assessed. CONCLUSION: Important subgroups, such as women, elderly men, diabetic patients and ethnic minorities, are under-represented in outpatient cardiac rehabilitation, although they benefit similarly to other patients. Due to lower baseline quality of life, women may need special medical attention prior to outpatient cardiac rehabilitation.     

Characterization of Burkholderia pseudomallei isolated in Thailand and Malaysia

A total of 35 Burkholderia pseudomallei isolates from Thailand (16 clinical and eight soil isolates) and Malaysia (seven animal, two isolate each from clinical and soil) were investigated by their antimicrobial resistance, plasmid profiles and were typed by randomly amplified polymorphic DNA analysis. All isolates were found to be resistant to six or more of the 12 antimicrobial agents tested. Only two small plasmids of 1.8 and 2.4 megadalton were detected in two clinical isolates from Thailand. RAPD analysis with primer GEN2-60-09 resulted in the identification of 35 RAPD-types among the 35 isolates. The constructed dendrogram differentiated the 35 isolates into two main clusters and a single isolate. The wide genetic biodiversity among the 35 isolates indicate that RAPD-PCR can be a useful method to differentiate unrelated B. pseudomallei in epidemiological investigation.     

Pharmacokinetics of phenytoin in routine clinic patients in Malaysia*

We estimated individual and population Michaelis-Menten pharmacokinetic parameters for phenytoin (DPH) in epileptic patients attending our neurology clinic using the computer programme. OPT®. Our results agreed well with literature values but were lower than those we obtained earlier in a smaller number of patients. The K_m was independent of age, weight and sex but there was a weak, correlation between V_m and body weight. We conclude that the use of population V_m and K_m in normograms could lead to errors in DPH dose estimations as they correlated very poorly with patient characteristics. OPT® was easy to use and sufficiently accurate for deriving dose estimates in routine patients. Its use would enable practitioners to generate their patients' own parameters for use in individual dosage adjustments. The estimates can subsequently be updated as more data become available.     

The epidemiology of pneumococcal carriage and infections in Malaysia

In Malaysia, various aspects of the epidemiology of pneumococcal carriage and disease remain largely unclear due to the lack of supporting data. Although a number of relevant studies have been documented, their individual discrete findings are not sufficient to inform experts on pneumococcal epidemiology at a national level. Therefore, in this review we aim to bring together and systematically evaluate the key information regarding pneumococcal disease epidemiology in Malaysia and provide a comprehensive overview of the data. Major aspects discussed include pneumococcal carriage, disease incidence and prevalence, age factors, invasiveness of pneumococci, serotypes, molecular epidemiology and antibiotic susceptibility. Penicillin resistance is increasingly prevalent and studies suggest that the majority of pneumococcal serotypes causing pneumococcal disease in Malaysia are covered by currently available conjugate vaccines. Continued surveillance is needed to provide a better understanding of pneumococcal epidemiology in Malaysia.     

A critical review of the nursing shortage in Malaysia

BARNETT T., NAMASIVAYAM P. & NARUDIN D.A.A. (2010) A critical review of the nursing shortage in Malaysia. International Nursing Review 57 , 32–39
Objective:  This paper describes and critically reviews steps taken to address the nursing workforce shortage in Malaysia.
Background:  To address the shortage and to build health care capacity, Malaysia has more than doubled its nursing workforce over the past decade, primarily through an increase in the domestic supply of new graduates.
Methods:  Government reports, policy documents and ministerial statements were sourced from the Ministry of Health Malaysia website and reviewed and analysed in the context of the scholarly literature published about the health care workforce in Malaysia and more generally about the global nursing shortage.
Results:  An escalation in student numbers and the unprecedented number of new graduates entering the workforce has been associated with other impacts that have been responded to symptomatically rather than through workplace reform. Whilst growing the domestic supply of nurses is a critical key strategy to address workforce shortages, steps should also be taken to address structural and other problems of the workplace to support both new graduates and the retention of more experienced staff.
Conclusion:  Nursing shortages should not be tackled by increasing the supply of new graduates alone. The creation of a safe and supportive work environment is important to the long-term success of current measures taken to grow the workforce and retain nurses within the Malaysian health care system.     

The epidemiology of pneumococcal carriage and infections in Malaysia

In Malaysia, various aspects of the epidemiology of pneumococcal carriage and disease remain largely unclear due to the lack of supporting data. Although a number of relevant studies have been documented, their individual discrete findings are not sufficient to inform experts on pneumococcal epidemiology at a national level. Therefore, in this review we aim to bring together and systematically evaluate the key information regarding pneumococcal disease epidemiology in Malaysia and provide a comprehensive overview of the data. Major aspects discussed include pneumococcal carriage, disease incidence and prevalence, age factors, invasiveness of pneumococci, serotypes, molecular epidemiology and antibiotic susceptibility. Penicillin resistance is increasingly prevalent and studies suggest that the majority of pneumococcal serotypes causing pneumococcal disease in Malaysia are covered by currently available conjugate vaccines. Continued surveillance is needed to provide a better understanding of pneumococcal epidemiology in Malaysia.     

Australasian emergency physicians: A learning and educational needs analysis. Part six: Differences in confidence,exposure to learning and expressed learning needs by subgroups of Australasian emergency physicians

Objective: To determine differences in the confidence and learning needs between subgroups of Fellows of the Australasian College for Emergency Medicine (FACEM), according to sex, type of hospital of principal employment, region of practice in Australasia, year of obtaining the fellowship and percentage of hours worked clinically. Method: Mailed survey of all FACEM with multiple Likert scale options. Results: Male emergency physicians (EP) more often expressed confidence in 14 of 58 tasks, but female EP more often expressed a strong desire for continuing professional development (CPD) in 8. EP working in private hospitals were more likely to find lack of conference in their contracts a barrier to participation in CPD (28% [CI 14.1–47.8]vs 7.3% [CI 5.2–10.1]; P = 0.003). EP obtaining their fellowship before 1990 were more confident in 13 of 25 non‐clinical tasks than others but had similar confidence in clinical skills. Although EP who spent 30% or less on clinical work expressed confidence more frequently in a range of non‐clinical skills, they were less confident for paediatric emergencies, central lines, orthopaedics and tube thoracostomy. There were few variations between Australian states and territories and New Zealand in confidence of EP. EP in regional and rural centres nominated geographical factors (31.3% [CI 21.2–43.4]vs 17.2% [CI 13.9–21.3]; P = 0.012), other colleagues being at the same conference (46.9% [CI 35.2–58.9]vs 28.3% [CI 24.2–32.9]; P = 0.005) and inability to use their conference leave (48.4% [CI 36.6–60.4]vs 33.1% [CI 28.7–37.8]; P = 0.024) as significant barriers more frequently than their city colleagues. Conclusion: These findings might assist planning CPD for EP.     

Incidence of genetic subgroups of hereditary spinocerebellar ataxia in Fukushima Prefecture

The prevalence of each type of hereditary spinocerebellar ataxias (SCAs) was genetically determined in Fukushima Prefecture, and the results were compared to those in other areas of Japan. The genetic analyses were done in 29 patients with dominant SCA and 5 patients with SCA with negative family history. Machado-Joseph disease was identified in 41.3% of the cases, SCA6 17.2%, dentatorubral-pallidoluysian atrophy (DRPLA) 6.9% and unknown 34.5%. The incidence is clearly different from those of Miyagi and Yamagata Prefectures as SCA1 has not been identified in our region, and is in fact similar to that of Hokuriku or Kanto Provinces. An apparent difference in the incidence of each SCA may be attributed to the historical and geographic regional difference in the distribution of inhabitants and also to the small size of the SCA population we have so far investigated. In addition, 2 of the 3 genetically identified DRPLA in this study were not clinically diagnosed, and one of them was thought to be sporadic. Late onset DRPLA may thus be misdiagnosed to other disease categories, when dementia was not apparent at the time of onset.