Surveillance and resistance status of Aedes population in two suburban residential areas in Kampar town, Perak, Malaysia.

In this study, 13 weeks (October to December 2012) of ovitrap surveillance was conducted in two suburban residential areas in Kampar town, Perak. A total of 17,310 Aedes mosquitoes were found in Taman Kampar Jaya, whereas Taman Juloong recorded a higher number at 19,042. Less than 1% of these were identified as Aedes aegypti, with the remaining confirmed as Aedes albopictus. The female Ae. albopictus were subsequently subjected to WHO standard diagnostic test kits against two pyrethroids (0.05% deltamethrin and 0.75% permethrin) and two organophosphates (1% fenitrothion and 5% malathion). The Ae. albopictus from both research sites were the most susceptible to deltamethrin, recording KT50 and KT95 response values of 15.84 minutes and 16.18 minutes; and 48.18 minutes and 49.44 minutes respectively. This was followed by permethrin (20.57 minutes and 17.52 minutes; 29.54 minutes and 54.54 minutes) and malathion (48.46 minutes and 62.69 minutes; 87.72 minutes and 141.04 minutes). Fenitrothion was found to be least effective towards Ae. albopictus; recording KT50 and KT95 response values of 150.29 minutes and 293.41 minutes for Taman Kampar Jaya, and 203.32 minutes and 408.07 minutes respectively for Taman Juloong. All tested Ae. albopictus showed 100% mortality after 24 hours post exposure. As both residential areas were fogged periodically by the municipal council; alternating between organophosphates and pyrethroids, thus, constant monitoring is crucial in light of the emergence of resistance noted in Ae. albopictus towards fenitrothion.

Tartrate-resistant acid phosphatase isoform 5a as an inflammation marker in end-stage renal disease.

AIM: End-stage renal disease (ESRD) is often complicated by chronic inflammation and malnutrition. We tested whether serum tartrate-resistant acid phosphatase (TRACP) isoform 5a relates to other markers of inflammation in ESRD. MATERIAL: Predialysis serum was collected from 99 ESRD patients (51 male, 48 female) aged 55 +/- 15 years and a control group of 36 healthy subjects (8 male, 28 female) aged 43.2 +/- 10.5 years. METHODS: Serum TRACP 5a activity and protein, TRACP 5b activity and C-reactive protein (CRP) were estimated by in-house immunoassays. Commercial kits were used for serum bone-specific alkaline phosphatase, Ntelopeptides of Type I collagen, interleukin-6 (IL-6) and fetuin-A. Intact parathyroid hormone was determined by chemiluminescent assay. Albumin, cholesterol, triglycerides, ferritin and hemoglobin were compared to the hospital reference ranges. Bone mineral density (BMD) was measured at the heel in 69 patients and all control subjects and expressed as g/cm2 and age-corrected T-score. RESULTS: Mean (median) levels of all serum markers were significantly elevated in ESRD except fetuin-A, which was significantly reduced. Mean BMD (g/cm2) was not different than control, but mean T-score was significantly reduced. TRACP 5a protein correlated with CRP, triglycerides and ferritin, but not with IL-6 or any other nutritional or bone markers or BMD. TRACP 5b activity correlated with all bone markers and BMD, but not with inflammation or nutritional markers. CONCLUSION: Our findings suggest that TRACP 5a may be a useful marker to estimate the degree of inflammation in ESRD patients on chronic hemodialysis.

Role of polymorphisms of the inflammatory response genes and DC-SIGNR in genetic susceptibility to SARS and other infections.

1. A genetic risk-association study involving more than 1200 subjects showed individuals homozygous for L-SIGN tandem repeats are less susceptible to SARS infection. 2. This was supported by in vitro binding studies that demonstrated homozygous L-SIGN, compared to heterozygous, had higher binding capacity for SARS coronavirus (SARS-CoV), with higher proteasome-dependent viral degradation. In contrast, homozygous L-SIGN demonstrated lower binding capacity for HIV1-gp120.3. Genetic-association studies for single nucleotide polymorphisms of the inflammatory response genes, namely TNF-alpha, INF-alpha, INF-beta, INF-gamma, IL1-alpha, IL1-beta, IL-4, IL-6 and iNOS, failed to show a significant association with SARS clinical outcomes or susceptibility.

Outbreak of human metapneumovirus infection in psychiatric inpatients: implications for directly observed use of alcohol hand rub in prevention of nosocomial outbreaks.

Nosocomial outbreaks of infectious diseases in psychiatric facilities are not uncommon but the implementation of infection control measures is often difficult. Here, we report an outbreak of an acute respiratory illness in a psychiatric ward between 29 July and 20 August 2005 involving 31 patients. Human metapneumovirus was detected in seven (23%) patients by reverse transcription-polymerase chain reaction and nucleotide sequencing. A review of outbreak surveillance records showed that six nosocomial outbreaks occurred in the year 2005, of which four (67%) were confirmed or presumably related to a respiratory viral infection. Directly observed deliveries of alcohol hand rub 4-hourly during daytime to all psychiatric patients was instituted in December 2005. Only one nosocomial respiratory viral outbreak occurred in the following year. The total number of patients and staff involved in nosocomial outbreaks due to presumed or proven respiratory virus infections decreased significantly from 60 to six (P<0.001), whereas those due to all types of nosocomial outbreaks also decreased from 70 to 24 (P=0.004). Alcohol hand rub has been shown to have potent bactericidal and virucidal activity against a wide range of nosocomial pathogens. Regular use of directly observed alcohol hand rub may decrease the incidence and scale of nosocomial outbreaks due to enveloped respiratory viruses especially in mentally incapacitated patients.

Long-term dentofacial changes in Chinese obstructive sleep apnea patients after treatment with a mandibular advancement device.

The objective of this study was to evaluate long-term dentofacial changes in Chinese obstructive sleep apnea (OSA) patients treated with a mandibular advancement device (MAD). Lateral cephalograms in natural head posture were obtained from 67 consecutive OSA patients (mean age = 46.9 +/- 8.9 years) treated with an MAD. The cephalograms were obtained at start of treatment (T0), after 1 year (T1), 2 years (T2), and 3 years (T3) of treatment. The lateral cephalograms were digitized twice, and the average of two readings was used for statistical analyses. Small, but statistically significant changes occurred in some dentofacial variables. The lower anterior facial height steadily increased during the observation period, and this increase was significant for the T0-T1 and T1-T2 periods and marginally significant for the T2-T3 period. A significant increase in the mandibular plane angle was observed during the T0-T1 and T2-T3 periods only. Significant reductions in the overjet and overbite were observed for the T0-T1 period but not thereafter. Statistically significant dentofacial changes were observed in this study, but they were of small magnitude. The overjet and overbite changes observed mainly occurred at the initial stage of treatment.

Impact of severe respiratory syndrome on anxiety levels of front-line health care workers.

OBJECTIVE: To identify anxiety levels among front-line health care workers during the 2003 severe acute respiratory syndrome outbreak. DESIGN: Questionnaire survey. SETTING: Regional hospital, Hong Kong. PARTICIPANTS: All hospital staff were given a questionnaire; administrative staff who had not had any patient contact served as controls. MAIN OUTCOME MEASURES: Levels of contact with patients who had severe acute respiratory syndrome were measured and correlated with anxiety levels as determined by the State-Trait Anxiety Inventory. RESULTS: Of 4252 questionnaires distributed between May and June 2003, 2040 (48.0%) were returned and 1926 (45.3%) were valid for analysis. Overall, 534 (27.7%) respondents had had contact with patients with severe acute respiratory syndrome. Anxiety scores ranged from 20 to 80, and mean (standard deviation) scores were higher among staff who had had contact with patients with severe acute respiratory syndrome than among those who had not (52.6 [10.5] versus 49.8 [10.1], respectively; P<0.01). Mean anxiety levels were higher among workmen, health care assistants, and nurses than among administrative staff controls or doctors (P<0.01). Anxiety scores were correlated with burnout scores (Pearson's correlation coefficient, 0.52-0.59) and with discomfort from wearing protective gear (0.21-0.32). CONCLUSION: Severe acute respiratory syndrome has likely stressed the public health care system. Prediction and early identification of adverse factors in a crisis situation would allow early implementation of interventions to reduce and counteract the impact of this stress.

Peripartum tuberculosis as a form of immunorestitution disease.

The aim of this study was to assess the clinical spectrum of peripartum tuberculosis from the perspective of immunorestitution disease. Of 29 patients with peripartum tuberculosis, 27 (93.1%) had extrapulmonary tuberculosis, 20 (69%) of whom were affected in the central nervous system. Twenty-two (75.9%) patients had no clinical features suggestive of tuberculosis during pregnancy. The median time from delivery to the onset of immunorestitution was 4 days, but treatment with anti-tuberculous therapy was delayed for a median time of 27 days after the onset of symptoms. Despite therapy, 11 (38%) patients died and 4 (13.8%) had residual functional deficits. Peripartum tuberculosis is an important differential diagnosis of postpartum fever (of unknown origin) without localized signs.

Coronavirus as a possible cause of severe acute respiratory syndrome.

BACKGROUND: An outbreak of severe acute respiratory syndrome (SARS) has been reported in Hong Kong. We investigated the viral cause and clinical presentation among 50 patients. METHODS: We analysed case notes and microbiological findings for 50 patients with SARS, representing more than five separate epidemiologically linked transmission clusters. We defined the clinical presentation and risk factors associated with severe disease and investigated the causal agents by chest radiography and laboratory testing of nasopharyngeal aspirates and sera samples. We compared the laboratory findings with those submitted for microbiological investigation of other diseases from patients whose identity was masked. FINDINGS: Patients' age ranged from 23 to 74 years. Fever, chills, myalgia, and cough were the most frequent complaints. When compared with chest radiographic changes, respiratory symptoms and auscultatory findings were disproportionally mild. Patients who were household contacts of other infected people and had older age, lymphopenia, and liver dysfunction were associated with severe disease. A virus belonging to the family Coronaviridae was isolated from two patients. By use of serological and reverse-transcriptase PCR specific for this virus, 45 of 50 patients with SARS, but no controls, had evidence of infection with this virus. INTERPRETATION: A coronavirus was isolated from patients with SARS that might be the primary agent associated with this disease. Serological and molecular tests specific for the virus permitted a definitive laboratory diagnosis to be made and allowed further investigation to define whether other cofactors play a part in disease progression.

Pyothorax-associated large B-cell lymphoma: case report with emphasis on the potential diagnostic challenge.

A rare case of pyothorax-associated large B-cell lymphoma occurring in Hong Kong is reported. The patient was a 64-year-old Chinese male who presented with shortness of breath and pleuritic pain. Radiological examination revealed left pleural thickening associated with bilateral pleural effusion. Open biopsy of the thickened parietal pleura revealed occasional large malignant lymphoid cells of B lineage admixed with fibrin and hyalinised fibrous tissue. These lymphoma cells were shown to harbour both Epstein-Barr virus and human herpesvirus type 8 by in situ hybridisation and immunohistochemical study, respectively. There was no associated lymphadenopathy and hepatosplenomegaly. The clinicoradiological presentation and pathological findings thus fulfilled the criteria of the so-called pyothorax-associated large B-cell lymphoma. Awareness of this rare entity, together with diligent histological examination and proper application of ancillary investigative techniques, are essential for making a correct diagnosis. The co-infection with Epstein-Barr virus and human herpesvirus type 8 in this case also suggests a possible pathogenetic relationship between pyothorax-associated large B-cell lymphoma and primary effusion lymphoma.

Hospital re-admission in patients with acute exacerbation of chronic obstructive pulmonary disease.

A retrospective study was carried out in a Hong Kong regional hospital with 24-h emergency service, to study the factors associated with shorter time to re-admission after acute exacerbation of chronic obstructive pulmonary disease (COPD). From 1 January 1997 to 31 December 1997, the first admission (index admission) of each patient through the emergency room with COPD/chronic bronchitis/emphysema was included. A total of 551 patients fulfilled the inclusion criteria. The total acute and rehabilitative length of stay (mean +/- SD) was 9.41+/-11.67 days. Within 1 year after discharge, 327 patients (59 35%) were re-admitted at least once. Median time to first re-admission after discharge was 240 days. By Cox regression analysis, the following factors were independently associated with shorter time to re-admission: hospital admission within 1 year before index admission, total length of stay in index admission > 5 days, nursing home residency, dependency in self-care activities, right heart strain pattern on electrocardiogram, on high dose inhaled corticosteroid and actual bicarbonate level > 25 mmol l(-1). These factors may be relevant in the future planning of healthcare utilization for COPD patients.

Physiological regulation of the immunological synapse by agrin.

T cell activation is dependent on both a primary signal delivered through the T cell receptor and a secondary costimulatory signal mediated by coreceptors. Although controversial, costimulation is thought to act through the specific redistribution and clustering of membrane and intracellular kinase-rich lipid raft microdomains at the contact site between T cells and antigen-presenting cells. This site has been termed the immunological synapse. Endogenous mediators of raft clustering in lymphocytes have not been identified, although they are essential for T cell activation. We now demonstrate that agrin, an aggregating protein crucial for formation of the neuromuscular junction, is also expressed in lymphocytes and is important in reorganization of membrane lipid microdomains and setting the threshold for T cell signaling. Our data show that agrin induces the aggregation of signaling proteins and the creation of signaling domains in both immune and nervous systems through a common lipid raft pathway.

Naphthol-ASBI phosphate as a preferred substrate for tartrate-resistant acid phosphatase isoform 5b.

Tartrate-resistant acid phosphatase (TRAP) isoform 5b is a potential serum marker for osteoclastic activity. Biochemical assays for serum TRAP activity with para-nitrophenylphosphate (pNPP) have low specificity for bone because of hydrolysis by unrelated nontype 5 TRAPs of blood cells and by related isoform 5a. Our purpose was to increase the specificity of TRAP assay for osteoclastic activity by using naphthol-ASBI phosphate (N-ASBI-P) as a substrate for serum type 5 TRAP activity and heparin as an inhibitor of isoform 5a. TRAP activity in individual and pooled sera of normal subjects and patients with endstage renal disease (ESRD) and rheumatologic diseases was quantitated using pNPP and N-ASBI-P as substrate at pH 5.5 and 6.1. For some experiments, heparin (23U/ml) was added as a specific inhibitor of isoform 5a activity. Isoforms 5a and 5b were separated from serum pools by cation exchange chromatography and identified by nondenaturing polyacrylamide gel electrophoresis (PAGE). N-ASBI-P was selectively hydrolyzed by TRAP isoform 5b. TRAP assays with pNPP and N-ASBI-P correlated only in ESRD sera, which contained primarily isoform 5b. The two assays did not correlate in normal or rheumatic sera with significant amounts of 5a. Heparin inhibited isoform 5a activity approximately 50% but had little effect on isoform 5b activity. Biochemical assay of serum TRAP activity can be made specific for isoform 5b by using N-ASBI-P and heparin. This method can be adapted to simple microplate biochemical or immunochemical assays. This simplified method for assessment of osteoclastic TRAP 5b activity warrants a detailed investigation in diseases of bone metabolism.

Tartrate-resistant acid phosphatase isoform 5b as serum marker for osteoclastic activity.

BACKGROUND: Tartrate-resistant acid phosphatase (AcP) 5b is a marker of osteoclastic activity and bone resorption. Immunoassays for serum TRAcP may lack sensitivity and specificity because of the presence of non-bone isoform 5a. The purpose of this study was to isolate the serum isoforms, quantify their disease-related expressions, and test an improved immunoassay for TRAcP 5b. METHODS: We separated TRAcP isoforms chromatographically from pooled sera of healthy, rheumatoid arthritis (RA) and endstage renal disease (ESRD) subjects. TRAcP isoforms were identified by electrophoresis and quantified by biochemical and immunochemical assays. Serum TRAcP activity in healthy, RA, and ESRD cohorts was assessed at pH 5.5 and 6.1, and compared with bone alkaline phosphatase (BAP) and N-telopeptides of type I collagen (NTx). RESULTS: TRAcP isoforms 5a and 5b were present in all sera; 5b was identical to osteoclastic TRAcP. In serum from healthy subjects, 5a accounted for 87% of the enzyme protein but only 55% of the activity. In RA, both isoforms were increased two- to threefold in protein, but their specific activities were subnormal. In ESRD, only 5b was abnormal, being increased fivefold in protein and threefold in activity. In RA sera, TRAcP activity did not correlate with either BAP or NTx. In ESRD sera, TRAcP activity correlated with BAP and NTx only when measured at pH 6.1. CONCLUSIONS: All sera contained both TRAcP isoforms 5a and 5b, but only 5b was present in bone. TRAcP isoform expression was variable in different diseases. Measurement of TRAcP activity at pH 6.1 improves the specificity of immunoassay for isoform 5b.

Electrophoretic study of tartrate-resistant acid phosphatase isoforms in endstage renal disease and rheumatoid arthritis.

The objective of this study was to identify the isoform, type-5a or type-5b, responsible for increased tartrate-resistant acid phosphatase (TRAP) activity in endstage renal disease (ESRD) and TRAP protein in rheumatoid arthritis (RA). We studied 24 sera each from healthy, ESRD and RA subjects. Type-5 TRAP activity and protein were quantitated by immunoassays. Isoform expression was determined by computerized imaging of non-denaturing polyacrylamide gels (PAGE) stained for TRAP activity. Other biochemical markers included: intact parathyroid hormone (iPTH), total and bone-specific alkaline phosphatase (TAP, BAP), N-telopeptides of type-I collagen (NTx), and free pyridinoline (Pyd). Isoform 5a was normal in both ESRD and RA. Isoform 5b was elevated in ESRD only. Serum TRAP activity correlated with both isoforms 5a and 5b in RA, but only with 5b in ESRD. TRAP protein assays did not correlate with PAGE assays for 5a or 5b. TRAP activity, but not protein, correlated with BAP and NTx in RA sera. Both TRAP activity and protein correlated with iPTH, TAP and Pyd in ESRD sera. Increased TRAP activity in ESRD was due to increased osteoclastic isoform 5b and related to bone turnover. Increased TRAP protein in RA was suspected, but not proven, to be isoform 5a and not related to bone turnover. Heterogeneity of serum TRAP and preferential expression of isoforms has clinical significance in different diseases including ESRD and RA.

Use of non-invasive positive-pressure ventilation for acute respiratory failure: prospective study.

OBJECTIVE: To study the effectiveness and safety of non-invasive positive-pressure ventilation in the management of acute respiratory failure. DESIGN: Prospective study. SETTING: Regional public hospital, Hong Kong. PATIENTS: One hundred and eighty-nine haemodynamically stable adult Chinese patients with acute respiratory failure (119 men and 70 women; mean age, 71.2 years [range, 18-92 years]) who were treated with non-invasive positive-pressure ventilation as the primary mode of ventilatory assistance from 1 January 1996 to 31 December 1998. MAIN OUTCOME MEASURES: Arterial blood gas measurements, respiratory rate, airway pressures used, use of endotracheal intubation, and standardised mortality ratio. RESULTS: Fifty-two patients had hypoxaemic respiratory failure (group I); 97 had hypercapnic respiratory failure (group II); and 40 had either type with advanced co-morbidities and were not planned to receive endotracheal intubation (group III). For groups I and II, the overall mean duration of non-invasive positive-pressure ventilation was 56.2 hours. Improvements in gas exchange were seen in approximately 71% of these patients, endotracheal intubation was not needed for 82%, and the standardised mortality ratio was 0.86. The hospital survival rate was approximately 93% in non-intubated patients and 41% in intubated patients. Predictors of success were reduction in respiratory rate within 6 hours (P<0.005), and (for hypercapnic respiratory failure) increased pH and reduced arterial carbon dioxide tension within 24 hours (P<0.005). Patients with pneumonia had significantly higher failure rates (P<0.05). Group III patients were older, had higher Acute Physiology and Chronic Health Evaluation II scores, and required longer ventilatory support, but their gas exchange response rate was 68%. The only complication of treatment was minor facial skin abrasions. CONCLUSION: Non-invasive positive-pressure ventilation is effective in treating haemodynamically stable patients with acute respiratory failure and causes few and minor complications.

Clinical significance of immunoassays for type-5 tartrate-resistant acid phosphatase.

BACKGROUND: Tartrate-resistant acid phosphatase (TRAP; EC 3.1.3.2) is a product of osteoclasts and a biochemical marker of bone resorption rate. However, erythrocytes and platelets contribute to total TRAP activity in serum, reducing the specificity of direct biochemical assays in serum. Osteoclast TRAP is also known as type-5 TRAP and is antigenically unique. Immunoassays are sought to improve the specificity and sensitivity of TRAP as a bone marker. METHODS: We developed two colorimetric microplate assays for type-5 TRAP: an enzyme capture immunoassay to measure antibody-bound enzymatic activity, and a two-site immunoassay to measure bound enzyme protein. Both use the same monoclonal antibody (14G6) to capture type-5 TRAP, which permits determination of specific activity of serum TRAP in health and disease. RESULTS: Both TRAP assays were linear from one-tenth to fivefold the mean value in 18 healthy subjects. In these subjects, the mean (SD) TRAP activity was 3.2 (0.54) U/L for the enzyme capture assay and 37 (13) microg/L for the two-site assay. Mean TRAP activity was not significantly increased in 64 patients with endstage renal disease requiring hemodialysis (HD) or 99 unselected patients with rheumatic diseases. By contrast, TRAP protein was increased in both the HD and rheumatic disease groups. The specific activity of TRAP in the 17 of 64 HD sera that had increased TRAP activity (0.088 U/microg) was similar to that in healthy subjects (0.091 U/microg). By contrast, the specific activity of TRAP in the 31 of 99 rheumatic sera with increased TRAP protein (0.035 U/microg) was significantly decreased. CONCLUSIONS: Wide sample distributions for TRAP activity in HD patients and TRAP protein in rheumatic disease patients suggest the presence of subpopulations of HD patients with increased TRAP activity and of rheumatic patients with increased TRAP protein. Each assay for TRAP activity and protein may have its own biological significance and clinical applications in specific groups of patients.

Computed tomography guidance in bone marrow aspiration for diagnosis of marrow necrosis and metastasis.

Bone marrow necrosis is most frequently diagnosed at postmortem examination. Antemortem diagnosis is still uncommon. We illustrate four cases where initial bedside attempts at needle aspiration and biopsy of primary and metastatic tumor tissue from the sternum were complicated by inadequate specimen retrieval secondary to marrow necrosis and/or tissue destruction by tumor. In these cases, CT guidance was useful in the precise localization of the bulk of the tissue mass and consequently the successful retrieval of adequate diagnostic specimens. We demonstrate CT guidance as an excellent and convenient alternative in circumstances where adequate marrow aspirations and biopsies are difficult and complicated.

Acute promyelocytic leukemia. New methods in diagnosis and treatment.

Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia characterized by hypergranular leukemic cells, bleeding diathesis and t(15; 17) translocation. The t(15; 17) translocation leads to the production of the PML-RAR alpha fusion protein which plays a vital role in the pathogenesis of APL by arresting normal differentiation of myeloid precursors. However, in the presence of high concentrations of all-trans-retinoic acid (ATRA), the PML-RAR alpha fusion protein serves to stimulate cell differentiation. The diagnosis of APL and the detection of residual disease are based on the t(15; 17) translocation. Treatment with a combination of ATRA and anthracycline-AraC chemotherapy has shown a higher rate of complete remission in APL. We report the case of a 71-year-old male with the rare microgranular variant of APL to illustrate these findings. The patient was treated with a combination of ATRA and Daunorubicin-AraC chemotherapy and achieved complete remission. He developed retinoic acid syndrome as a complication of therapy with ATRA. The methods for diagnosis, the molecular mechanisms in the oncogenesis of APL, rationale of treatment of APL with ATRA, complications of therapy and the new concepts in the treatment of ATRA-resistant APL are discussed.