Lurasidone-Induced Manic Switch in an Adolescent with Bipolar I Disorder: a Case Report.

Lurasidone is used for treatment of bipolar depression in adults and adolescents. Lurasidone-associated manic switch has been reported in adults but not yet in adolescents. We report a case of lurasidone-induced manic switch in a male adolescent treated for bipolar I depression. Five days after adding lurasidone to his regimen (sodium valproate and olanzapine), our patient became manic with psychotic features. After discontinuation of lurasidone, he was stabilised with electroconvulsive therapy, and the medication was switched to a lithium-quetiapine combination. This case highlights the potential risk of lurasidone-induced manic switch in adolescents with bipolar depression.

Is dengue a threat to the blood supply?

Dengue is the most common arthropod-borne infection worldwide, affecting at least 50 million people every year and endemic in more than 100 countries. The dengue virus is a single-stranded RNA virus with four major serotypes. Infection with one serotype confers homotypic immunity but not heterologous immunity, and secondary infection with another serotype may lead to more severe disease. The major route of transmission occurs through the Aedes aegypti mosquito vector, but dengue has also been transmitted through blood transfusion and organ transplantation. Infection results in a spectrum of clinical illness ranging from asymptomatic infection, undifferentiated fever, dengue fever, dengue haemorrhagic fever (DHF) to dengue shock syndrome (DSS). Dengue is spreading rapidly to new areas and with increasing frequency of major outbreaks. A trend has also been observed towards increasing age among infected patients. This will impact blood supply availability as more blood donors are deferred because of dengue infection or exposure to infection. The risk of transmission through transfusion of blood from asymptomatic viraemic donors will also increase. Although screening tests for dengue and effective pathogen reduction processes are now available for the blood supply, the value of implementing these costly measures needs to be carefully considered. Demand for platelets and fresh frozen plasma will rise with increasing number of DHF/DSS. Evidence-based guidelines for the clinical use of these blood components in the management of patients with DHF/DSS have not been well established, and inappropriate use will contribute to the challenges faced by blood services.

Blood transfusion requirements and independent predictors of increased transfusion requirements among adult patients on extracorporeal membrane oxygenation -- a single centre experience.

BACKGROUND/OBJECTIVES: More adults undergo extracorporeal membrane oxygenation (ECMO) now. They have high transfusion requirements. This study described transfusion requirements of adults during ECMO in a single institution, and determined factors associated with high transfusion requirements. MATERIALS/METHODS: Retrospective analysis was done on the amount of blood products received by adults during ECMO. Predictors of increased average daily transfusion requirements during ECMO and increased ECMO duration (which correlated positively with total transfusion requirements) were determined. RESULTS: Forty-one patients (median age 50 years) underwent 42 ECMO sessions for respiratory failure (16.7%), cardiogenic shock (76.2%) or massive pulmonary embolism (7.1%). They received 569 red blood cells, 852 platelets, 126 fresh-frozen plasma (FFP) and 220 cryoprecipitate in total during median ECMO duration of 5 (1-15) days. On multivariate analysis, average daily red blood cell transfusion increased with nadir haemoglobin (Hb) during ECMO (Hb(nadir)) of < 7.5 g/dl (P < 0.001). Average daily platelet transfusion increased with recent antiplatelet agents (P = 0.015) and maximum Hb decline of > 5.5 g/dl during ECMO (P = 0.011). Average daily platelet transfusion > 3 units was also associated with increased ECMO duration (P = 0.024). Average daily FFP transfusion was increased in patients with hypertension (P = 0.007) and Hb(nadir) < 7.5 g/dl (P = 0.050). Patients with sepsis (P = 0.009) or without surgery (P = 0.009) had increased ECMO duration, which correlated positively with total transfusion requirements during the entire ECMO session. ECMO improved mortality of patients with fulminant myocarditis, respiratory failure and massive pulmonary embolism. CONCLUSION: Adult ECMO patients with lower Hb(nadir) require more daily red blood cell and FFP. Hypertension increases daily FFP requirements. Recent antiplatelet agents, larger Hb decline and longer ECMO duration increase daily platelet requirements. Patients with sepsis or on ECMO for medical reasons have longer ECMO duration, which is associated with total transfusion requirements. Some of these factors may be identified early to optimize blood product support.

Knowledge and perceptions regarding colorectal cancer screening among Chinese--a community-based survey in Singapore.

OBJECTIVE: Despite the increase in colorectal cancer (CRC) incidence among Chinese in Asia, there are no data on predictors of CRC screening uptake in this population. This study investigated how knowledge and perceptions about CRC correlated with screening behavior in Singaporean-Chinese. METHODS: A community-based cross-sectional study was carried out on Singaporean-Chinese at least 50 years old in Queenstown Estate, Singapore between 1/1/2006 and 1/2/2006. A questionnaire administered via face-to-face interviews elicited knowledge, perceptions and screening behavior of subjects. RESULTS: The response rate was 72.4%, with 514 completed responses. Expense was the commonest perceived barrier to screening (56.6% agreed), unlike for other populations. Social influence is important, with 67.5% agreeing to the statement "I would go for CRC screening if my family wanted me to". After excluding confounders, Chinese who had been for fecal occult blood test (FOBT) screening had higher knowledge score (p<0.001), lower perceived severity (p<0.01), were more likely to have been influenced by their family/friends to go for screening (p=0.04) and to have attended screening tests for other diseases (p<0.001). CONCLUSION: FOBT screening uptake is associated with specific areas of knowledge and perception among Singaporean-Chinese. To increase screening uptake within Chinese populations, clinicians should consider these factors in their approach to patients.

Transforming growth factor beta-1 and gene polymorphisms in oriental ankylosing spondylitis.

OBJECTIVES: To study serum levels of transforming growth factor beta-1 (TGFbeta1) and the expression of TGFbeta1 in in vitro peripheral blood mononuclear cell (PBMC) cultures in oriental ankylosing spondylitis (AS) patients, and to determine their association with codon 10 and 25 TGFB1 gene polymorphisms. METHODS: Serum levels of TGFbeta1 were measured by enzyme-linked immunosorbent assay (ELISA). The ability of PBMCs to synthesize TGFbeta1 and other cytokines was assessed by in vitro cultures stimulated with mitogen. Genomic DNA was extracted from PBMCs of AS patients (n=72) or unrelated healthy controls (n=96). The codon 10 and 25 polymorphisms in the TGFB1 gene were analysed using standard polymerase chain reaction-based methods. RESULTS: AS patients had significantly higher serum TGFbeta1 levels than controls (P<0.001). There was no difference in the distribution of codon 10 and 25 TGFB1 genotypes between AS patients and controls. Incubation of AS and control PBMC with phytohaemagglutinin (PHA) led to upregulation of TGFbeta1, interleukin-10, tumour necrosis factor-alpha (TNFalpha) and interferon-gamma (IFNgamma) assessed by ELISA. Importantly, PHA-induced TGFbeta1 production was significantly enhanced in AS patients compared with normal controls whereas the production of the pro-inflammatory cytokines TNFalpha and IFNgamma was reduced. CONCLUSIONS: Our results show that AS patients express significantly higher levels of serum TGFbeta1 independent of the codon 10 and 25 genotype. Activation of AS PBMCs led to enhanced TGFbeta1 production accompanied by reduction of TNFalpha and IFNgamma while the converse was observed in normal controls.

Spontaneous cerebrospinal fluid otorrhoea via oval window: an obscure cause of recurrent meningitis.

Spontaneous cerebrospinal fluid (CSF) leak via the oval window is uncommon and can result in recurrent bacterial meningitis. Current understanding of spontaneous CSF otorrhoea is reviewed and a diagnostic algorithm is presented. A seven-year-old boy presented with bilateral congenital deafness and recurrent meningitis. High-resolution computed tomography (HRCT) of the temporal bone showed a labyrinthine deformity and communication between the internal auditory canal (IAC) and the cochlea. Subtotal petrosectomy with closure of the external acoustic meatus and eustachian tube was performed. Post-operatively, the child had no further episodes of meningitis. This rare and obscure cause of recurrent childhood meningitis requires a high index of suspicion and the use of diagnostic tools, especially HRCT.

Head and neck cancer after foreign body ingestion.

INTRODUCTION: Ingestion of a foreign body is a common occurrence in our population. We present 2 cases that illustrate an unusual outcome of an otherwise usual occurrence. CLINICAL PICTURE: Two patients who presented with a history of ingestion of fish bones were worked up. The radiological findings were suspicious of a foreign body and both underwent examination under general anaesthesia. The endoscopic findings were normal. After further evaluation for persistent calcifications with computed tomography, a thyroid malignancy was found in the first patient and tongue cancer in the second patient. TREATMENT: The first patient underwent elective hemithyroidectomy and the second underwent wide excision of the tumour with neck dissection. OUTCOME: Both recovered uneventfully with regular follow-up in the outpatient clinic. CONCLUSION: There should be a high index of suspicion in patients with persistent calcifications.

Transmission of tuberculosis from patient to healthcare workers in the anaesthesia context.

INTRODUCTION: Pulmonary tuberculosis (PTB) is prevalent in our population. We report an incident of healthcare workers (HCWs) suspected of being infected by a patient with undiagnosed active PTB in the operating theatre. CLINICAL PICTURE: A 60-year-old patient admitted for intestinal obstruction, underwent an emergency laparotomy. Preoperative chest X-ray (CXR) showed diffuse reticular-nodular shadowing and postoperative sputum was positive for acid-fast bacilli. TREATMENT: The patient was isolated and treated for active tuberculosis. The anaesthetist and her assistants in the operating theatre that day were referred to the infectious disease physician and some were started on tuberculosis prophylaxis. OUTCOME: The patient and the HCWs involved recovered. CONCLUSION: Thus, all PTB-susceptible patients with suggestive CXR should be treated as potentially infective. Adequate personnel protection should include highly efficient facemasks and shields. Risk of patient-to-patient transmission of tuberculosis through the anaesthetic circuit is low if effective bacterial/viral filters are used.

New strategies for the diagnosis and screening of malaria.

Thin and thick blood film microscopy are the "gold standard" for malaria diagnosis. In recent years, there have been important developments in malaria diagnostic tests including fluorescence microscopy of malaria parasites stained with acridine orange, dipstick immunoassays that detect species-specific parasite antigens, and more recently, detection of parasite nucleic acids after amplification by PCR. With some of these methods, sensitivities and specificities approaching and even exceeding those of the thin and thick film can be attained. In particular, PCR-based tests for plasmodium DNA or RNA are more sensitive and specific than other tests for malarial parasites. A specific application for PCR diagnosis of malaria could be blood donor screening. Clinical trials of blood donor sreening for malarial parasites by PCR are being conducted, in which pooled donor samples are screened to increase efficiency and reduce costs. Some of the new diagnostic methods may have specific applications in particular settings, depending on the purpose and location of testing, and other factors such as cost, desired sensitivity and specificity, speed and ease of use.

Failure of routine HIV-1 tests in a case involving transmission with preseroconversion blood components during the infectious window period.

CONTEXT: Current screening practices for blood donations have been successful in reducing human immunodeficiency virus (HIV) transmission through receipt of contaminated blood products. However, HIV-infected blood donations made prior to seroconversion and before high levels of viral replication occur could test negative using both serologic antigen and antibody tests. Testing based on nucleic acid amplification (NAT) is being implemented to screen for HIV-infected blood donated during this period, yet the issue of single vs minipool donation screening remains unresolved. OBJECTIVES: To determine HIV-1 genetic linkage between virus in 2 HIV-1-infected recipients of blood components and virus in the donor, who was HIV antigen and antibody negative at the time of donation; to screen the blood donor's plasma with HIV NAT assays, including those currently proposed for use in US blood donation screening. DESIGN AND SETTING: Case study conducted in October 1997 involving the Communicable Disease Centre, Singapore General Hospital, and the Singapore Blood Transfusion Service, Singapore. SUBJECTS: The blood donor and the 2 recipients of donor platelets and red blood cells. MAIN OUTCOME MEASURES: Genetic analysis of the HIV-1 p17 coding region of gag and the C2V5 region of env to determine the genetic relatedness of virus from the donor and recipients; reactivity in quantitative and qualitative assays, and reactivity in donor screening HIV NAT assays in single donation and minipool screening contexts. RESULTS: Direct DNA sequencing demonstrated identical HIV-1 subtype E viral sequences in the donor and recipients. Based on comparisons of a qualitative and quantitative assay for HIV-1 RNA levels, a low level of viremia (range, 5-39 copies/mL in plasma) was estimated to be in the donor's undiluted blood at the time of donation. Additional testing using donor-screening NAT assays showed consistent detection of HIV RNA in the undiluted donor plasma whereas detection was inconsistent at the 1:16 and 1:24 dilution levels currently used in minipool screening of blood donations in the United States. CONCLUSIONS: Transmission of HIV from a blood donor to a platelet recipient and a red blood cell recipient occurred in the preseroconversion infectious window period. The viral load in the implicated donation was estimated to be less than 40 copies/mL of plasma. Current US minipool HIV NAT screening protocols may not be sufficiently sensitive to detect all infectious window-period donations. JAMA. 2000;284:210-214

The appropriate use of antineutrophil cytoplasmic antibody (ANCA) testing in rheumatic diseases.

The antineutrophil cytoplasmic antibody (ANCA) test is now available in most routine diagnostic immunology laboratories. Improvement, simplification and standardisation of the testing methodology have enabled it to become more reliable and accessible to clinicians. ANCA has strong association with and is most useful in the diagnosis and management of the ANCA-associated vasculitides which include Wegener's granulomatosis, microscopic polyarteritis, Churg-Strauss syndrome and primary pauci-immune necrotising and crescentic glomerulonephritis. It is found in lower frequency in the other vasculitides and collagen vascular diseases, in chronic inflammatory bowel disease and autoimmune liver disease, and in miscellaneous infective and neoplastic disorders. While the gold standard for ANCA testing remains the indirect immunofluorescence (IIF) assay, identification of ANCA-specific antigens such as proteinase 3 and myeloperoxidase has enabled the development of antigen-specific tests. The antigen-specific solid-phase assays have comparable sensitivity with IIF assays and improved specificity in some instances. However, appropriate use of the ANCA test requires full knowledge of its capabilities and limitations, and the results should always be correlated with clinical data. In particular, it is important to understand that it is not only test sensitivity and specificity, but patient selection that contributes to the positive predictive value and clinical relevance of the test result.

Confirmatory serological testing of blood donors positive on TPHA screening in Singapore.

Seventy-two blood donors who were tested positive by the Singapore Blood Transfusion Service (SBTS) for Treponema pallidum haemagglutination (TPHA) test, were evaluated at the Department of Sexually Transmitted Diseases Clinic (DSC) between November 1994 to December 1996. All underwent syphilis serological testing, including rapid plasma reagin test (RPR), TPHA test and fluorescent treponemal antibody-absorption (FTA-Abs) test. All except one (98.6%) were confirmed TPHA positive by the DSC. Of the 71 TPHA-confirmed-positive donors, 53 (74.6%) were subsequently tested positive for FTA-Abs and 18 (25.4%) were tested negative for FTA-Abs. Twenty-two (31%) of the 71 TPHA-positive blood donors had reactive RPR and 49 (69%) had non-reactive RPR. Of the 22 TPHA-positive donors who had reactive RPR, 19 (86%) had positive FTA-Abs (13 late latent syphilis, 4 serological scar, one late congenital syphilis, one secondary syphilis), and 3 (14%) had negative FTA-Abs (all late latent syphilis). Of the 49 TPHA-positive donors who had non-reactive RPR, 34 (69%) had positive FTA-Abs (24 late latent syphilis, 9 serological scar, one late congenital syphilis) and 15 (31%) had negative FTA-Abs (12 late latent syphilis, 2 serological scar, one false-positive TPHA). Only one TPHA-positive donor referred by the SBTS subsequently turned out to have negative syphilis serology at the DSC. Overall, 68 (95.8%) TPHA-positive donors who had a past history of sexual exposure were managed as treated or untreated syphilis, regardless of their RPR or FTA-Abs results. However, FTA-Abs was found to be useful in the management of 3 (4.2%) TPHA-positive blood donors in the absence of a history of sexual exposures.

Racial differences in Helicobacter pylori seroprevalence in Singapore: correlation with differences in peptic ulcer frequency.

The aim of this study was to determine, first, whether racial differences exist in the seroprevalence of Helicobacter pylori infection in Singapore, and second, whether these differences correlate with racial differences in peptic ulcer frequency. A commercial serological test for immunoglobulin (Ig)G antibody to H. pylori which was 90% sensitive and 83% specific in our population was used to screen 403 adult blood donors of Chinese, Malay and Indian origin, aged between 15-60 years. Serum specimens from 84 paediatric patients admitted to the Paediatrics Department, National University of Singapore, with non-gastroenterological illnesses were also tested. In all three races, seroprevalence of H. pylori increased with age. Indians have the highest prevalence of infection followed by Chinese and Malays. Peptic ulcer prevalences are known to be highest in Chinese, followed by Indians and Malays. The Malays have the lowest prevalence of H. pylori and peptic ulcer among the three races in Singapore. Indians have a higher prevalence of H. pylori antibodies but a lower frequency of peptic ulcer than the Chinese. Racial differences in peptic ulcer frequency between Chinese and Indians are not explained by the prevalence of H. pylori infection; other environmental or genetic factors may be involved.

A study of treponema pallidum haemagglutination positive blood donors in Singapore.

The Treponema Pallidum Haemagglutination (TPHA) test has been used for screening of syphilis among blood donors in Singapore since September 1992. Among the 79 500 donations that were screened between September 1992 and December 1993, 191 were tested positive (incidence rate of 0.24%). Seventy-two donors (37.7%) were evaluated at the Department of Sexually Transmitted Disease Control clinic. Seventy-nine percent of these donors had high risk sexual exposure and 33.3% had a history of sexually transmitted diseases. Eighty-three percent of the donors were diagnosed to have late latent syphilis, 9.7% were diagnosed to have a serological scar and the remaining had secondary syphilis, early latent syphilis and a false positive reaction. At least 65.3% of these donors would have been missed if the reagin test was used alone as the screening test. Thus, the TPHA test is a good marker for screening those who have high risk sexual behaviour and it is a more sensitive test than the reagin test for screening blood donors.

Genetic polymorphism within HLA-A*02: significant allelic variation revealed in different populations.

HLA-A2 is present at high frequency in most populations, as identified by serological and biochemical means. The value of these methods is limited by their failure to discriminate between the products of the 14 known allelic HLA-A*02 variants. The great majority of genetic polymorphism which defines the allelic variants is found in exons 2 and 3 of the A*02 genes. These exons encode the alpha-1 and alpha-2 domains of the HLA Class I molecules, and variation within the genes may influence the peptide binding specificity of the gene products of each allele. Failure to accurately assign the allelic types has implications in transplantation, in interpretation of cellular assays and in the understanding of HLA disease associations. We have developed a method for determining the 14 known alleles of HLA-A*02 by use of ARMS-PCR to determine the degree of variation of HLA-A*02 alleles in 3 different population groups. Considerable variation was found in the relative frequencies of particular A*02 alleles between Caucasian, oriental and black individuals. Our results indicate the importance of ethnic origin in terms of the expected HLA-A*02 allelic profile, and emphasize the functional significance of allele specific subtyping of HLA-A*02.