Incomplete Kawasaki Disease in a 44-day-old baby.

Kawasaki disease (KD) is an acute systemic vasculitis usually affecting children <5 years old. We report a 44-dayold baby who had persistent fever despite being on antibiotics for presumed sepsis. Erythema of Bacillus Calmette-Guerin (BCG) scar and thrombocytosis were noted on day-2 of illness. Diagnosis of incomplete KD was made on the 10th day of illness. Her fever resolved with intravenous immunoglobulin, but echocardiogram revealed coronary artery aneurysm. High index of suspicion is required to diagnose KD in infants ≤3 months since it is rare and commonly presents with incomplete clinical features. The presence of unexplained fever for ≥5 days with erythema of BCG scar or thrombocytosis in infants should alert the clinicians of KD.

A Review of Acute Rheumatic Fever and Rheumatic Heart Disease Research in Malaysia.

A total of 39 titles related to rheumatic fever or rheumatic heart disease in Malaysia were found with online literature search dating back to their inceptions and through 2014. Additional publications from conference journals were included. Nine papers were selected based on clinical relevance and future research implications. There were no population-based studies on the incidence or prevalence of ARF or RHD. In the 1980s, the incidence of admission due to ARF ranged from 2 to 21.1 per 100 000 paediatric admission per year. The burden of disease was significant in the adult population; 74.5% of patients with RHD were female, of which 77.1% were in the reproductive age group of 15-45 years old. Rheumatic mitral valve disease constituted almost half (46.7%) of all mitral valve repairs, ranging from 44.8 - 55.8 patients per year from 1997 - 2003. From 2010-2012, mitral valve interventions increased to 184 per year, of which 85.7% were mitral valve repair. In children with ARF, 25.4% - 41.7% had past history of rheumatic fever or RHD. In patients with rheumatic mitral valve disease undergoing surgical or medical interventions, only 6% reported history of ARF, none had history of GABHS pharyngitis or antibiotic prophylaxis. Only 44.7% of patients with RHD on follow-up were on intramuscular benzathine penicillin prophylaxis. Overall, there is scarcity of publications on ARF and RHD in Malaysia. Priority areas for research include determination of the incidence and prevalence of ARF and RHD, identification of high-risk populations, evaluation on the implementation and adherence of secondary preventive measures, identification of subclinical RHD especially amongst the high-risk population, and a surveillance system to monitor and evaluate preventive measures, disease progression and outcomes.

Salmonella enteritidis ventriculitis.

Salmonella sp are important causes of meningitis among neonates and young children in Malaysia. We present a case of Salmonella enteritidis meningitis in a six week old female who presented with a one week history of fever, diarrhea and seizures which was unsuccessfully treated with a third generation cephalosporin. She had a relapse of meningitis complicated with ventriculitis and hydrocephalus, requiring an eleven week course of meropenem. She improved clinically, but did not have improvement in the cerebrospinal fluid (CSF) glucose level despite prolonged antibiotic use. This case illustrates the dilemma in determining the duration of antibiotic needed to successfully treat Salmonella enteritidis ventriculitis.

Epidemiology and strain characterization of rotavirus diarrhea in Malaysia.

OBJECTIVES: The objectives of the study were to describe the epidemiology and strain characterization of rotavirus (RV), to determine the proportion of hospitalizations for diarrhea attributable to RV among children under 5 years of age, and to estimate the disease burden of RV diarrhea in Malaysia. METHODS: All children 0-59 months of age admitted for acute gastroenteritis to Kuala Lumpur Hospital (KLH) or Hospital Umum Sarawak (HUS) were surveyed. The periods of surveillance were from February 1, 2001 to April 30, 2003 in KLH and April 1, 2001 to March 31, 2003 for HUS. RESULTS: The highest rate of RV-associated diarrhea was among children aged 6-17 months, accounting for 55% of RV-associated diarrhea. There was no seasonality observed in either hospital. P[8]G9 strains were predominant, accounting for 73% of all strains in both hospitals, 80% from KLH and 61% from HUS. There was no mortality. CONCLUSIONS: RV was responsible for 38% of hospitalizations for diarrhea. It was most common in the 6-17 months age group. There was no seasonality observed for RV-associated diarrhea. The most prevalent strain of RV was P[8]G9. The estimated incidence of RV-associated diarrhea was 27 per 10000 population under the age of 5 years per year.

Improved colonoscopy success rate with a distally attached mucosectomy cap.

BACKGROUND AND STUDY AIMS: Although colonoscopy is a well-established procedure, various technical difficulties may cause failure. This report describes experience with cap-assisted colonoscopy (CAC), a technique in which a mucosectomy cap is attached to the end of colonoscope in order to improve the success rate. PATIENTS AND METHODS: From January 2003 to May 2005, CAC was used in consecutive patients with difficult colonoscopy procedures, which were defined firstly as failure to pass through the sigmoid colon after 20 min of examination, or secondly as failure to reach the cecum at the end of the procedure. Patients with prior colonic surgery, poor bowel preparation, distal colonic stricture, or obstructing tumors were excluded. The results with the CAC method were reviewed retrospectively. RESULTS: A total of 100 patients met the criteria for difficult colonoscopy during the study period. When CAC was used to repeat the procedure, cecal and terminal ileal intubation could then be achieved in 94 and 70 patients, respectively. In the remaining six patients in whom cecal intubation failed, one failure was due to a tumor obstruction at the splenic flexure. CONCLUSIONS: CAC can be used as a rescue method to improve the success rate of colonoscopy when failure is encountered.

Accuracy of endoscopic ultrasonography in diagnosing ascites and predicting peritoneal metastases in gastric cancer patients.

BACKGROUND: Preoperative diagnosis of peritoneal metastases (PM) is difficult in patients with gastric cancer (GC). AIMS: To assess the accuracy of endoscopic ultrasonography (EUS) in diagnosing ascites and its predictability for the presence of PM in GC patients. SUBJECTS: Consecutive patients with newly diagnosed GC from 1998 to 2004 were studied. METHODS: All patients underwent EUS, ultrasound (US), and computed tomography (CT) scan for preoperative staging and the presence of ascites. The results were compared with operative findings. The diagnosis of PM was confirmed by histopathology or peritoneal fluid cytology. RESULTS: A total of 301 patients were recruited and in 250 patients the presence of ascites (n = 93) and PM (n = 71) were confirmed. EUS was more sensitive (87.1%) than combined US and CT scan examinations (16.1%) and operative findings (laparoscopy or laparotomy) (40.9%) in diagnosing ascites. Sensitivity, specificity, positive and negative predictive values, and accuracy for predicting the presence of PM were 73%, 84%, 64%, 89%, and 81% by EUS; 18%, 99%, 87%, 75%, and 76% by combining US and CT scan; and 77%, 94%, 83%, 91%, and 89% by operative findings, respectively. In multivariate logistic regression analysis, EUS detected ascites was the only significant independent predictor for the presence of PM (p<0.001; odds ratio 4.7 (95% confidence interval 2.0-11.2)). CONCLUSION: EUS is a sensitive method for diagnosing ascites which is an important predictive factor for the presence of PM in GC patients.

Genotype C hepatitis B virus infection is associated with an increased risk of hepatocellular carcinoma.

BACKGROUND: Identification of risk factors for the development of hepatocellular carcinoma (HCC) is important for HCC surveillance in chronic hepatitis B virus (HBV) infection. Our aim was to study the independent risk factors and effect of HBV genotypes on HCC development in a prospective longitudinal cohort of chronic hepatitis B patients. PATIENTS AND METHODS: Chronic hepatitis B patients recruited since 1997 were prospectively followed up for the development of HCC. HCC was diagnosed by a combination of alpha fetoprotein, imaging, and histology. Liver cirrhosis was defined as ultrasonic features of cirrhosis together with hypersplenism, ascites, varices, and/or encephalopathy. RESULTS: In total, 426 patients were followed up for 1664 person years; median 225 (range 12-295) weeks. Forty nine (11%) patients had underlying clinical liver cirrhosis. A total of 242 (57%) and 179 (42%) patients had HBV genotypes C and B, respectively. Twenty five patients developed HCC in a median follow up of 121 (range 14-236) weeks. The overall incidence of HCC was 1502 cases per 100 000 person years. On multivariate analysis, clinical liver cirrhosis and HBV genotype C infection were independently associated with HCC development, with an adjusted relative risk of 10.24 (95% confidence interval (CI) 4.39-23.89; p<0.001) and 2.84 (95% CI 1.05-7.72; p = 0.040), respectively. Patient age, sex, hepatitis B e antigen (HBeAg) status, alanine aminotransferase (ALT) levels, and basal core promoter mutations did not predict HCC development. Patients infected with HBV genotype C tended to have persistently positive HBeAg or fluctuating HBeAg status and higher ALT levels during the follow up period. CONCLUSION: Genotype C HBV infection is an independent risk factor for HCC development in addition to liver cirrhosis.

Pharmacokinetic study of levofloxacin in rat blood and bile by microdialysis and high-performance liquid chromatography.

The aim of this study was to develop a rapid and sensitive method for the simultaneous determination of unbound levofloxacin in rat blood and bile using high-performance liquid chromatography coupled with microdialysis for further pharmacokinetic study. Microdialysis probes were simultaneously inserted into the jugular vein toward the right atrium and the bile duct of male Sprague-Dawley rats for biological fluid sampling after administration of levofloxacin 3 mg/kg through the femoral vein. Levofloxacin and dialysates were separated using a Merck LiChrospher reversed-phase C18 column maintained at ambient temperature. The mobile phase was comprised of acetonitrile-1 mM 1-octanesulfonic acid (40:60, v/v, pH 3.0 adjusted with orthophosphoric acid). The fluorescence response for levofloxacin was observed at excitation and emission wavelengths of 292 and 494 nm, respectively. The detection limit of levofloxacin was 50 ng/ml. Intra-day and inter-day precision and accuracy of levofloxacin measurements fell well within the predefined limits of acceptability. The disposition of levofloxacin in the blood and bile fluid suggests that there was rapid exchange and equilibration between the blood and hepatobiliary systems, and the plasma level of levofloxacin was greater than that of the bile. Thus, levofloxacin undergoes hepatobiliary excretion but might not be related to the P-glycoprotein transport system.

Determination and pharmacokinetic profile of omeprazole in rat blood, brain and bile by microdialysis and high-performance liquid chromatography.

The disposition and biliary excretion of omeprazole was investigated following i.v. administration to rats at 10 mg/kg. We used a microdialysis technique coupled to a validated microbore HPLC system to monitor the levels of protein-unbound omeprazole in rat blood, brain and bile, constructing the relationship of the time course of the presence of omeprazole. Microdialysis probes were simultaneously inserted into the jugular vein toward right atrium, the brain striatum and the bile duct of the male Sprague-Dawley rats for biological fluid sampling after the administration of omeprazole (10 mg/kg) through the femoral vein. The concentration-response relationship from the present method indicated linearity (r2>0.995) over a concentration range of 0.01-50 microg/ml for omeprazole. Intra-assay and inter-assay precision and accuracy of omeprazole fell well within the predefined limits of acceptability. Following omeprazole administration, the blood-to-brain coefficient of distribution was 0.15, which was calculated as the area under the concentration versus time curve (AUC) in the brain divided by the AUC in blood (k=AUCbrain/AUCblood). The blood-to-bile coefficient of distribution (k=AUCbile/AUCblood) was 0.58. The decline of unbound omeprazole in the brain striatum, blood and bile fluid suggests that there was rapid exchange and equilibration between the compartments of the peripheral and central nervous systems. In addition, the results indicated that omeprazole was able to penetrate the blood-brain barrier and undergo hepatobiliary excretion.

Effectiveness of family care intervention program on activity of daily living among disabled patients.

The objective of this prospective study was to compare the improvement of activity of daily living (ADL) scores between two groups of disabled patients who participated in a family care intervention program. 137 patients were selected from health stations and Activity of Daily Living (ADL) scores were assessed eight times over a period of 22 weeks. Family caregivers were trained to provide home nursing care for the disabled. The patients were divided into two groups: early-stage (intervention started less than 6 months from diagnosis) and late-stage (intervention started 7-24 months from diagnosis). Over the duration of the intervention program, the results, using ANCOVA test, showed that the ADL score of the early-stage had group increased by 12.9, compared to the later-stage group, which increased by 3.0 (p < .000). At one-year follow-up, the ADL score of the early-stage group increased by a greater extent (6.2) than the later-stage group (1.3). The factors that affected ADL scores of the survivals were as follows: age, baseline ADL score and duration of disability. The authors conclude that the intervention program was most effective in improving ADL score when intervention was implemented early.

An improved system for quantifying AgNOR and PCNA in canine tumors.

BACKGROUND: Quantifying silver stained nucleolar organizer regions (AgNORs) and proliferation cell nuclear antigens (PCNA) are useful techniques to measure proliferative activity of tumor cells; however, the nonspecific deposition of stains and overlappings of AgNOR and PCNA counts between grades of tumors hamper their applications. MATERIALS AND METHODS: Fifty-two surgical specimens from dogs, including mast cell tumors, perianal gland tumors and hyperplasias, fibromas, fibrosarcomas, and normal tissues were studied. The 3 microns dewaxed sections of formalin-fixed tissues were stained to detect AgNORs by a modified inverted incubation technique in a newly developed silver staining device. Data were collected and analyzed using a high-resolution digital microscope camera and image analysis software. Sequential sections were also stained for PCNA using an immunohistochemical method. RESULTS: The improved system for quantifying AgNOR provided more accurate and non-overlapping mean AgNOR counts, which enable us to distinguish benign states from malignant changes. The mean AgNOR cut-off points that discriminated grade II or III mast cell tumors from grade I, perianal gland carcinomas from adenomas (or hyperplasia), fibrosarcomas from non-fibrosarcoma tissues, were 6.0, 14.1, 9.4, and 8.8 respectively. The mean AgNOR areas, relative AgNOR areas, and PCNA positive rates of some malignant and non-malignant tissues (benign tumor and normal tissues) were significantly different (P < 0.05). CONCLUSIONS: This improved system is a sensitive and rather precise method for quantifying the AgNOR and PCNA. It provides a valuable objective measurement for differentiating benign and malignant tumors.

Simultaneous blood and brain sampling of cephalexin in the rat by microdialysis and microbore liquid chromatography: application to pharmacokinetics studies.

To circumvent the need for laborious sample clean-up and multiple blood sampling, a system was developed consisting of on-line microdialysis coupled to microbore liquid chromatography and ultraviolet detection. The system was designed for the simultaneous and continuous monitoring of unbound blood and brain cephalexin in the rat following single bolus intravenous administrations (10 mg/kg, n = 6). Microdialysis probes were inserted into the jugular vein and brain striatum, respectively, for blood and brain sampling. Chromatographic conditions consisted of a mobile phase of methanol-100 mM monosodium phosphoric acid (20:80, v/v, pH 5.0) pumped through a microbore reversed-phase column at a flow-rate of 0.05 ml/min. Detection wavelength was set at 260 nm. The method was validated for response linearity as well as intra- and inter-day variabilities. Rapid appearance of cephalexin in the striatal dialysate suggested good blood-brain barrier penetration. This study provided pharmacokinetics information for cephalexin as well as demonstrated the applicability of this continuous sampling method for pharmacokinetics studies.

Pattern of congenital heart disease and access to tertiary cardiac care in Malaysia.

This prospective, descriptive study was carried out to determine the pattern and the type of congenital heart disease seen in the Paediatric Departments in 4 government hospitals. The accessibility of surgical or transcatheter interventional treatment was also assessed. Consecutive new patients seen for suspected congenital heart disease from 1/1/95 till 31/12/95 (Group I) were registered. Records of patients seen from 1/1/95 to 31/8/95 (Group Ia) were reviewed 6 months after presentation to determine the nature of treatment received. Group II were cardiac patients who were first seen prior to the year 1995 and had undergone cardiac surgery or transcatheter interventional procedures in 1995. Of the 375 patients registered in the 4 hospitals, 250 were new patients and 125 were patients first seen prior to 1995 and had surgery or transcatheter interventional procedures in 1995. Of the 250 new patients, 83.2% had acyanotic cardiac lesions and 16.8% had cyanotic lesions. Ventricular septal defect was the commonest lesion, constituting 37.2%, followed by patent arterial duct (18.8%) and atrial septal defects (9.6%). At 6 month review, access to close-heart surgery or transcatheter interventional treatment were readily available. However, for patients with ventricular septal defects, 42.1% who required closure were still waiting for surgery 6 months after presentation. Of the 4 patients with Fallot's Tetralogy who required surgery, 2 had modified Blalock-Taussig shunt and 2 were awaiting surgery. In 1995, a total of 204 cardiac procedures were performed, there were 114 (55.9%) open heart procedures, 50 (24.5%) surgical ligation of the arterial duct, 28 (13.7%) modified Blalock-Taussig shunts, 11 (5.4%) transcatheter duct occlusion and 1 (0.5%) balloon valvuloplasty. The mean age of Fallot's Tetralogy repair was 6.4 years. No corrective surgery was performed for patients with complex cardiac lesions from the 4 hospitals in 1995. In conclusion, the pattern of congenital heart disease was similar to that seen world wide. Except for patent arterial duct, access to surgical treatment was inadequate.

Measurement of hydroxyl radical in rat blood vessel by microbore liquid chromatography and electrochemical detection: an on-line microdialysis study.

Salicylic acid (0.5 mM) is used as a trapping reagent of hydroxyl radical, and the formed 2,3- and 2,5-dihydroxybenzoic acids were collected via an on-line microdialysis device from the blood vessels. This study revealed the use of a sensitive liquid chromatographic system with electrochemical detection for the determination of 2,3- and 2,5-dihydroxybenzoic acids. Mobile phase consisted of 0.1 M monochloroacetic acid, 10 mM EDTA, 0.5 mM sodium octylsulfate, 20% acetonitrile and 5% tetrahydrofuran in 1 l (pH 3.0 adjusted with 1 M NaOH), and the flow-rate of 0.05 ml/min were found to be optimum. Isocratic separation of these adducts on a microbore column (reversed-phase C18, 150x1 mm I.D., 5 microm) was achieved within 10 min. The optimal applied potential of dihydroxybenzoic acids was set at 750 mV based on a hydrodynamic study. This method has the detection limits of 1.3 pmol/ml (or 0.2 ng/ml) for 2,3- and 2,5-dihydroxybenzoic acids in Ringer solution (at signal-to-noise ratio=3).

Determination of unbound ceftriaxone in rat blood by on-line microdialysis and microbore liquid chromatography.

In vivo microdialysis was used to determine unbound ceftriaxone in rat blood. A microdialysis probe was inserted into the jugular vein/right atrium of Sprague-Dawley rats, and dose of 10 mg/kg ceftriaxone was then administered via the femoral vein. Dialysates were automatically collected and injected into a liquid chromatographic system via an on-line injector. Isocratic elution of ceftriaxone within 10 min was achieved using a microbore liquid chromatographic system. The chromatographic mobile phase consisted of methanol-100 mM monosodium phosphoric acid (15:85, v/v, pH 7.0). The wavelength of the UV detector was set at 280 nm. Intra- and inter-assay accuracy and precision of the assay were less than 15%. The detection limit of ceftriaxone was 20 ng/ml. The results suggest that unbound ceftriaxone in rat blood is best fit to a biexponential decay model.

Radon mitigation by depressurization of concrete walls and slabs.

A special laboratory, the Radioisotope Unit Radon Analysis Laboratory, has been built for the study of radon mitigation in high-rise buildings. Reduction of radon exhalation rate from concrete walls as a result of depressurizing the interior of the wall was studied by embedding tunnels in a wall and pumping away the radon in the wall. The reduction in exhalation rate was quantified against the applied depressurization, the separation of the tunnels, the depth of the tunnel, and the thickness of the wall. Results show that radon exhalation rate from a wall embedded with tunnels can be reduced significantly by applying depressurization. For example, the radon exhalation rate from a wall of 20 cm thickness containing tunnels separated by 0.7 m can be reduced by 60% at a depressurization of 67 kPa (20 in Hg). This paper summarizes the effect of depressurization and suggests practical ways of applying the technique in radon mitigation in high-rise commercial buildings.

Microdialysis study of biliary excretion of chloramphenicol and its glucuronide in the rat.

The biliary excretion of chloramphenicol and its glucuronide has been evaluated by use of a microdialysis probe linked to automatic on-line microbore high-performance liquid chromatography. The microdialysis probe was inserted into the bile duct between the liver and the duodenum; to avoid obstruction of the bile duct or bile salt waste, a shunt linear probe was used. After intravenous administration of chloramphenicol succinate (100 mg kg(-1)) the amounts of unbound chloramphenicol and its glucuronide in the bile microdialysate were recorded. According to the pharmacokinetic results disposition of chloramphenicol seems to fit a two-compartment model whereas that of chloramphenicol glucuronide fits a one-compartment model in rat bile. The area under the concentration-time curve for chloramphenicol glucuronide was twice that for chloramphenicol in rat bile duct. Clearance of chloramphenicol glucuronide was significantly higher than that of chloramphenicol in biliary excretion, indicating that chloramphenicol and its glucuronide are actively excreted into the bile.

Determination of unbound cefmetazole in rat blood by on-line microdialysis and microbore liquid chromatography: a pharmacokinetic study.

A specific and sensitive microbore liquid chromatographic method for the determination of unbound cefmetazole in rat blood was developed. A microdialysis probe was inserted into the jugular vein/right atrium of a Sprague-Dawley rat. Cefmetazole (10 mg/kg, i.v.) was then administered via the femoral vein. Dialysates were automatically injected into a liquid chromatographic system via an on-line injector. Isocratic elution of cefmetazole was achieved by LC-UV within 10 min. Intra- and inter-assay accuracy and precision of the assay were < or = 10%. The detection limit of cefmetazole was 20 ng/ml. Pharmacokinetic analysis of results indicated that unbound cefmetazole levels in rats best fit a biexponential decay model.

On-line microdialysis coupled with microbore liquid chromatography for the determination of unbound chloramphenicol and its glucuronide in rat blood.

On-line microdialysis coupled with microbore liquid chromatography was used to investigate the pharmacokinetics of chloramphenicol and its glucuronide in rat blood. A microdialysis probe was inserted into a jugular vein of male Sprague-Dawley rats. Chloramphenicol succinate (20 mg/kg, intravenously) was then administered via a femoral vein. Dialysates were automatically injected onto a LC system, via an on-line injector. Samples were eluted with a mobile phase containing acetonitrile-10 mM monochloroacetic acid (30:70, v/v, pH 3.0). The UV detector wavelength was set at 278 nm. The limit of quantitation for chloramphenicol was 10 ng/ml. The in vitro recoveries of chloramphenicol and chloramphenicol glucuronide at 500 ng/ml were 32.2+/-0.3% and 11.4+/-0.7%, respectively (n = 6). Intra- and inter-assay accuracy and precision of the analyses were < or =10% in the range of 0.01 to 5.0 microg/ml.