Micro-interdigitated electrodes genosensor based on Au-deposited nanoparticles for early detection of cervical cancer.

Genosensor-based electrodes mediated with nanoparticles (NPs) have tremendously developed in medical diagnosis. Herein, we report a facile, rapid, low cost and highly sensitive biosensing strategy for early detection of HPV 18 using gold-nanoparticles (AuNPs) deposited on micro-IDEs. This study represents surface charge transduction of micro-interdigitated electrodes (micro-IDE) alumina insulated with silica, independent and mini genosensor modified with colloidal gold NPs (AuNPs), and determination of gene hybridization for early detection of cervical cancer. The surface of AuNPs deposited micro-IDE functionalized with optimized 3-aminopropyl-triethoxysilane (APTES) followed by hybridization with deoxyribonucleic acid (DNA) virus to develop DNA genosensor. The results of ssDNA hybridization with the ssDNA target of human papillomavirus (HPV) 18 have affirmed that micro-IDE functionalized with colloidal AuNPs resulted in the lowest detection at 0.529 aM. Based on coefficient regression, micro-IDE functionalized with AuNPs produces better results in the sensitivity test (R2 = 0.99793) than unfunctionalized micro-IDE.

Electrolyte imbalance in infectious disease patients at King Abdulaziz Hospital, Jeddah.

Objectives: Infectious diseases are the common cause of morbidity and mortality among humans. Electrolyte imbalance occurs frequently in patients with infectious diseases. This study aims to identify electrolyte imbalances in hospitalised patients with infectious diseases. Methods: Two hundred and eighty-three patients with age mean 36.48 ± 18.86 years, consisting of 127 (53.4%) males, 111 (46.6%) females, enrolled in a retrospective cohort study carried out at the King Abdulaziz University Hospital, Jeddah, KSA from September to December 2020. All hospitalised patients with infectious diseases were included. Demographic data, comorbidity, and diagnosis were collected from patients' sheets. Serum levels of electrolytes (chloride, potassium, sodium), urea, and creatinine were collected at admission (period 1), during hospital stay (period 2), and at discharge (period 3). Levels were compared during different periods. Results: Most infectious diseases were viral infections (63.4%), while comorbidity was diabetes mellitus (7.1%). Serum chloride elevated from period 1 to period 3 (P = 0.046). Sodium elevated between period 1 and both period 2 and period 3 (P < 0.001). Urea decreased between period 1 and both period 2 (P = 0.018) and period 3 (P < 0.001). Creatinine decreased between period 1 and both period 2 and period 3 (P < 0.001) and between period 2 and period 3 (P < 0.001). Patients with decreased chloride and sodium levels were mostly in the 1st period, while those with decreased potassium levels were mostly in the period 2. Conclusion: Prevalence of electrolyte imbalance in hospitalised patients with an infectious disease at the King Abdulaziz University Hospital, Jeddah was high, especially at admission and during the hospital stay.

Designing DNA probe from HPV 18 and 58 in the E6 region for sensing element in the development of genosensor-based gold nanoparticles.

The E6 region has higher protuberant probability annealing than consensus probe focusing on another region in the human papillomavirus (HPV) genome in terms of detection and screening method. Here, we designed the first multiple virus single-stranded deoxyribonucleic acid (ssDNA) for multiple detections in an early phase of screening for cervical cancer in the E6 region and became a fundamental evolution of detection electrochemical HPV biosensor. Gene profiling of the virus ssDNA sequences has been carried by high-end bioinformatics tools such as GenBank, Basic Local Alignment Searching Tools (BLAST), and Clustal OMEGA in a row. The output from bioinformatics tools resulted in 100% of similarities between our virus ssDNA probe and HPV complete genome in the databases. The cross-validation between HPV genome and our designed virus ssDNA provided high specificity and selectivity during screening methods compared with Pap smear. The DNA probe for HPV 18, 5' COOH-GAT CCA GAA GGT ACA GAC GGG GAG GGC ACG 3', while 5'COOH-GGG CGC TGT GCA GTG TGT TGG AGA CCC CGA3' as DNA probe for HPV 58 designed with 66.77% guanine (G) and cytosine (C) content for both. Our virus ssDNA probe for the HPV biosensor promises high sensitivity, specificity, selectivity, repeatability, low fluid consumption, and will be useful in mini-size diagnostic devices for cervical cancer detection.

The Prevalence of Sensorineural Hearing Loss in ß-thalassaemia patient treated with Desferrioxamine.

OBJECTIVE: This study aimed to evaluate the prevalence of sensorineural hearing loss (SNHL) in ß-thalassaemia patients treated with Desferrioxamine (DFO) and determine the correlation of SNHL with average daily DFO dosage, serum ferritin level and Therapeutic index (T.I). METHODS: This is a cross sectional descriptive study carried out for a period of 14 months and 54 patients were recruited. The recruited patients are transfusion dependant ß- thalassaemia patient aged 3 years and above treated with DFO. An interview, clinical examination and hearing assessment, which included tympanogram, and Pure Tone Audiometry (PTA) or behaviour alaudiometry were performed. The data on age started on DFO, average daily DFO, duration of DFO intake, serum ferritin past 1 year and Therapeutic Index (T.I) were obtained from patients' case notes. RESULTS: The prevalence of SNHL was 57.4% and majority has mild hearing loss (93.6%). Fourteen patients (25.9%) have bilateral ear involvement and as many as 17 patients (31.5%) have SNHL in either ear. A total of 23 patients (42.6%) have normal hearing level. Although the prevalence of SNHL was 57.4%, only a small percentage of the patient noticed and complained of hearing loss (11.1%). There is no association between age started on DFO, average daily DFO and duration of DFO intake with normal hearing group and those patients with SNHL. Positive correlation was seen between average daily DFO with 2000 and 4000Hz on PTA in the left ear and between serum ferritin level past 1 year with 4000 and 8000Hz in the right ear and 8000Hz in the left ear. No significant correlation was seen between T.I on PTA. CONCLUSION: The prevalence of SNHL from hearing assessment is high in ß-thalassaemia patients in this study. However, it is manifested clinically in a smaller percentage. We suggest a baseline hearing assessment should be carried on all ß-thalassaemia patients prior to DFO chelation therapy.

Dynamic modeling of reversible methanolysis of Jatropha curcas oil to biodiesel.

Many kinetics studies on methanolysis assumed the reactions to be irreversible. The aim of the present work was to study the dynamic modeling of reversible methanolysis of Jatropha curcas oil (JCO) to biodiesel. The experimental data were collected under the optimal reaction conditions: molar ratio of methanol to JCO at 6 : 1, reaction temperature of 60°C, 60 min of reaction time, and 1% w/w of catalyst concentration. The dynamic modeling involved the derivation of differential equations for rates of three stepwise reactions. The simulation study was then performed on the resulting equations using MATLAB. The newly developed reversible models were fitted with various rate constants and compared with the experimental data for fitting purposes. In addition, analysis of variance was done statistically to evaluate the adequacy and quality of model parameters. The kinetics study revealed that the reverse reactions were significantly slower than forward reactions. The activation energies ranged from 6.5 to 44.4 KJ mol⁻¹.

Parenting Stress in Childhood Leukaemia

Parenting stress is the stress level experienced within the role of a parent (HoekstraWeebers et al. 1998). The source of stressors is variable and dependent on the phase of disease and chemotherapy (Sawyer et al. 2000). Failure to cope with these stressors may in turn affect the child’s emotional and social adjustment towards the diagnosis of cancer in addition to poor medical treatment adherence behaviour(Sawyer et al. 1993). The objectives of this study are to determine the level of parenting stress, the risk factors contributing to high parenting stress, and the coping mechanisms used to handle the stress. This single centred, cross-sectional study was done amongst 117 parents at the Paediatric Haematology and Oncology Unit, Universiti Kebangsaan Malaysia Medical Centre (UKMMC) over two years duration. Self-administered questionnaires comprising the Parenting Stress Index/Short Form (PSI/SF) and Coping Inventory for Stressful Situation (CISS) were distributed to parents of children who were 12 years old and below. The mean total parenting stress score amongst parents of children diagnosed with acute leukaemia was 91.5±21.1(95%CI). A total of 27.3% of parents experienced a high total parenting stress score(defined as total PSI score ≥ 75th centile, ie ≥ 103). Task-oriented coping mechanism was used by the majority of parents. Emotion-oriented coping mechanism was the only identifiable risk factor for high parenting stress score following multiple logistic regression analysis. A parent who used emotion-oriented coping mechanism was 7.1 times (95% Confidence Interval 1.2 to 41.4) more likely to have a high parenting stress score compared to a parent who used other coping mechanisms. By identifying these at-risk parents, appropriate counselling and psychological support may be offered early to alleviate the stress as well as assist in the coping and adjustment mechanisms of these parents.

Spectrum of infections in splenectomised thalassaemia patients.

Splenectomised thalassaemia patients are at risk of developing sepsis. As the infection may be life-threatening, treatment should be sought and given promptly. A retrospective study was performed amongst our thalassaemia major patients who were splenectomised. The vaccination status of each patient and the types of infections seen were reviewed to obtain a local perspective. In our cohort of 49 splenectomised patients, 25 patients required hospitalization for the treatment of infection. There were a total of 40 febrile episodes within this hospitalised group of which 27.5% were microbiologically documented infection with bacteraemia. The predominant causative organisms were gram negative rods and three patients succumbed to overwhelming septicaemic shock as a result of delayed presentation. Sixty percent of the febrile episodes were clinically documented infection and comprised mainly upper respiratory tract infections. Based on the spectrum of infections seen, there is a need to improve the patients' awareness level so that early treatment is sought. There is also a need to re-address the approach towards vaccination in this immunocompromised group of patients by administering a booster pneumococcal and influenza vaccination in an attempt to reduce morbidity.

Minimal Residual Disease Status in Childhood Acute Lymphoblastic Leukaemias by Flow Cytometry and Their Clinical and Haematological Features

Residual disease in patients with acute leukaemia indicates unfavorable prognosis. The evaluation of remission using flow cytometry allows a better estimation of minimal residual disease (MRD) after induction chemotherapy in childhood acute lymphoblastic leukaemia (ALL) cases. Patients in morphological marrow remission with presence of blast cells of less than 5%, may still have up to 1010 leukaemic cells. However with flow cytometric analysis, lower levels of the residual leukaemic cells (1 in 104 cells) can be detected and it can be used as a tool to predict relapse. This study compared the presenting clinical and haematological features of children with ALL and their residual disease status determined by flow cytometry. Analysis of their MRD status following remission-induction chemotherapy were done at day-28, week-12 and week-20. The cases were also followed up to five years, to determine their survival status. Their residual disease status by flow cytometric immunophenotyping was also compared with their bone marrow findings morphologically. Thirty-eight cases of precursor B-ALL in pediatric patients from UKM Medical Centre (UKMMC) were analyzed. There was no significant correlation between demographic, clinical and haematological features with MRD status at day-28. However, there was a significant correlation between MRD status by flow cytometry and by morphological marrow examination at week-12. Three cases showed persistent MRD findings until week-20 where two of the cases relapsed and died subsequently. Twenty four patients were still alive after five years of follow up.

Juvenile myelomonocytic leukaemia: a case series.

Juvenile myelomonocytic leukaemia (JMML), previously known as juvenile chronic myeloid leukaemia (JCML) is a rare, myelodysplastic - myeloproliferative disease typically presenting in early childhood. This disorder is difficult to distinguish from other myeloproliferative syndrome such as chronic myeloid leukaemia (CML) because of the similarities in their clinical and bone marrow findings. However, because of its unique biological characteristics such as absolute monocytosis with dysplasia, absence of Philadelphia chromosome or BCR-ABL fusion protein, hypergammaglobulinaemia and raised fetal haemoglobin level, this disorder does not satisfy the criteria for inclusion in the CML or chronic myelomonocytic leukaemia (CMML) group, as seen in adult patients. We describe a series of three patients with JMML, who had almost similar clinical and laboratory findings, and discuss the difficulty in the classification and treatment of the disease.

Growth velocity in transfusion dependent prepubertal thalassemia patients: results from a thalassemia center in Malaysia.

Growth impairment is commonly seen in children with thalassemia despite regular blood transfusions and desferrioxamine treatments. We investigated the growth velocity of 26 prepubertal patients with beta-thalassemia or HbE-beta thalassemia who were transfusion dependent aged between 2 and 13 years. The prevalence of impaired growth velocity (ie, growth velocity less than the third percentile) amongst the transfusion dependent prepubertal thalassemics was 57.7% compared to 19.2% in the control group. The mean height velocity of the thalassemics was 11.1% less than controls but this difference was not statistically significant (4.23cm/year vs 4.76cm/year, p = 0.08). The mean serum ferritin level of the thalassemics with a height < 3rd percentile was higher compared to those with a height > 3rd percentile (4,567.0 vs 2,271.0, p = 0.01). Our study showed that there was a high prevalence of impaired growth velocity amongst our transfusion dependent prepubertal thalassemics. This highlights the problem of inadequate chelation therapy, and compliance with chelation therapy amongst our patients. This study emphasizes the importance of monitoring growth parameters and optimal iron chelation therapy in these patients.

Piperacillin-tazobactam plus amikacin as an initial empirical therapy of febrile neutropenia in paediatric cancer patients.

INTRODUCTION: We evaluated piperacillin-tazobactam in association with amikacin in the initial empirical therapy of febrile neutropenic children. METHODS: An open-labelled, non-randomised, prospective trial to assess the efficacy and safety of this association was conducted from June 1, 2001 to December 31, 2002. Children and adolescents were treated for a haematological malignancy or a primary, refractory or relapsed solid tumour, and presented with febrile neutropenia. Patients received intravenous piperacillin-tazobactam (90 mg/kg/dose every eight hours) plus a single daily dose of amikacin at 15 mg/kg/day, maximum 250 mg. If fever persisted, second-line therapy with carbapenem was administered. Teicoplanin was added for gram-positive isolates or for unremitting fever after 48 hours, if clinically indicated. Amphotericin B was added at 96 hours, if fever and neutropenia persisted. RESULTS: 155 episodes of fever and neutropenia in 76 patients were evaluable. 40 (25.8 percent) episodes were a microbiologically-documented infection, 30 (19.4 percent) were clinically-documented, and 85 (54.8 percent) were unexplained fever. 77 (49.7 percent) episodes responded to piperacillin-tazobactam plus amikacin without a need for treatment modification. A higher success rate (63.5 percent) was observed in episodes with unexplained fever. The predominant pathogens isolated in our study were gram-negative organisms (70.7 percent). A mild gastrointestinal intolerance occurred in 35 out of 155 (22.6 percent) episodes. CONCLUSION: This study suggests that piperacillin-tazobactam plus amikacin presents a satisfactory efficacy and a good tolerance as initial empirical therapy for febrile neutropenic children.

Assessment of P-gp and MRP1 activities using MultiDrugQuant Assay Kit: a preliminary study of correlation between protein expressions and its functional activities in newly diagnosed acute leukaemia patients.

Multidrug resistance (MDR) is believed to be responsible for poor response of patients towards chemotherapy particularly patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). The best-characterized resistance mechanism is the one mediated by permeability-glycoprotein (P-gp) encoded by MDR1 gene, which is responsible for drug efflux. We studied P-gp and multidrug resistance-associated protein 1 (MRP1) expression and functional activities in 43 newly diagnosed acute leukemia cases (19 paediatric ALL cases and 24 adult AML cases). The expression and functional activities were examined using flow cytometry and MultiDrugQuant assay kit (involving calcein AM uptake and efflux). P-gp and MRP1 expression and its functional activities were observed in 68.4% of paediatric ALL. In adult AML cases, all cases expressed MRP1 and its functional activities but only 58.3% were positive for P-gp and its functional activities. We were able to show a significant correlation between the expression of the multidrug resistant protein (P-gp and MRP1) and their functional activity in adult AML and paediatric ALL samples.

Malignant pancreatic carcinoid tumour.

Pancreatic carcinoid tumours are rare, particularly within the paediatric population. The clinical presentation is largely dependent on the functionality of the tumour. Although the tumour is generally slow-growing, surgical resection is still the mainstay of curative treatment. Morbidity is, however, significantly contributed by secretion of excess hormones; in view of this, biotherapy is an important treatment strategy. Octreotide, a somatostatin analogue, has been shown to be successful in both symptomatic control and stability of tumour progression. We report a 12-year-old girl, who presented with hypertensive crisis, and showed good response to a combination of chemotherapy and octreotide.

Cefepime plus amikacin as an initial empirical therapy of febrile neutropenia in paediatric cancer patients.

INTRODUCTION: We evaluated the efficacy of cefepime in association with amikacin in the initial empirical therapy of febrile neutropenic children. METHODS: The study was an open-labelled, non-randomised prospective trial to assess the efficacy and safety of this association, from January 2003 to December 2003. Children and adolescents were treated for a haematological malignancy or a primary, refractory or relapsed solid tumour, and presented with febrile neutropenia. Patients received cefepime (50 mg per kg per dose every 8 hours for children weighing less than or equal to 40 kg; and 2 g every 8 hours for those weighing more than 40 kg) plus a single daily dose of amikacin at 15 mg per kg per day, up to a maximum 250 mg. If fever persisted, a second-line therapy with carbapenem was administered. Amphotericin B was added at 96 hours if fever and neutropenia persisted. RESULTS: 103 episodes of fever and neutropenia were evaluated in 54 patients. 18.4 percent of the episodes were microbiologically-documented infections, 24.3 percent were clinically documented, and 57.3 percent were episodes with unexplained fever. 54.4 percent of the episodes responded to cefepime plus amikacin without a need for treatment modification. A higher success rate (74.6 percent) was observed in episodes with unexplained fever. In all cases of persistent fever, the antibiotics were changed to carbapenem within 72 hours and all patients survived. One patient died because of culture-negative septic shock within 24 hours of admission. A mild gastrointestinal intolerance occurred in three patients. CONCLUSION: This study suggests that cefepime plus amikacin presents a satisfactory efficacy and a good tolerance as an initial empirical therapy for febrile neutropenic children.

Recurrent gastric inflammatory myofibroblastic tumour in a 13-year-old male.

A 13-year-old boy who had epigastric pain and pallor for 2 months and found to have an ulcerative mass in the stomach and underwent partial gastrectomy. A diagnosis of inflammatory myofibroblastic tumour (IMT) of the stomach was made on histological examination. Three years later, recurrence in the stomach, with invasion into the pancreas and hilum of the spleen was noted and was managed by wide wedge resection of the stomach, distal pancreatectomy and splenectomy. The patient has been recurrence-free for the past 2 years. Gastric IMT is an uncommon tumour in children with unpredictable prognosis.

Transient abnormal myelopoeisis in newborns with Down syndrome.

Transient abnormal myelopoeisis (TAM) is a haematological phenomenon commonly seen in newborns with Down syndrome. Although the majority show spontaneous resolution, this condition should not be dismissed too readily as there have been associated fatalities. Furthermore, even for those who do show spontaneous resolution, a significant percentage will develop acute megakaryoblastic leukaemia within the next few years of life. We report a series of four patients with TAM who presented with hepatosplenomegaly and leucocytosis detected on preliminary investigations.

Prolonged remission after splenectomy for refractory Evans syndrome--a case report and literature review.

We describe a patient with Evans syndrome (autoimmune hemolytic anemia and autoimmune thrombocytopenia) who was refractory to steroids and intravenous immunoglobulin. She responded to splenectomy and has remained in clinical remission for 3 years. In the majority of cases, splenectomy rarely induces a durable remission but it may be beneficial in a small group of patients, hence should be considered as alternative therapy in the management of these patients.

Case report post-splenectomy sepsis in thalassemic patients.

Thalassemia is the commonest hemoglobinopathy in Malaysia. Patients with thalassemia major are transfusion dependent, and a large proportion of them will require splenectomy. As this particular group of patients is immunocompromized, overwhelming sepsis is a recognized complication. We report a series of three patients who all developed intra-abdominal abscesses following splenectomy.

Abnormalities in lung function among multiply-transfused thalassemia patients: results from a thalassemia center in Malaysia.

The aim of this study was to: (1) determine the prevalence and patterns of lung dysfunction among transfusion dependent thalassemics; (2) determine the associated factors that might contribute to this problem. This was a cross-sectional study involving 66 patients with transfusion dependent thalassemia aged 10 years and above. All patients underwent physical examination, standardized pulmonary function tests including spirometry, lung volume, and the carbon monoxide diffusion capacity. A restrictive pattern of lung dysfunction was observed in 22 patients (33.3%) and none showed the presence of obstructive ventilatory impairment. A reduction in the carbon monoxide diffusion capacity (DLCO) was seen 87.9% of the patients, including 7.6% who had evidence of hypoxemia. Ten patients showed a reduction in the FEF25-75% although they did not fulfil the criteria for small airway disease. No correlation was found between lung dysfunction and serum ferritin levels in the patients. Restrictive lung dysfunction and diffusion impairment were the predominant abnormalities found in our cohort of patients.

Peginterferon alfa-2b and ribavirin in thalassaemia/chronic hepatitis C virus-co-infected non-responder to standard interferon-based.

We describe a patient with HbE-beta thalassaemia and chronic hepatitis C virus infection (genotype 1a) who was treated successfully with peginterferon alfa-2b and ribavirin, following failure to respond to standard interferon and ribavirin therapy. She had sustained virological response for nearly 24 months after completing peginterferon alfa-2b and ribavirin therapy. Transfusion requirements were significantly increased during combination therapy due to ribavirin-induced haemolysis. The adverse effects of interferon were well tolerated. Combination therapy with peginterferon alfa-2b and ribavirin maybe a feasible treatment option for a subset of thalassaemia/HCV infected non-responders to standard interferon-based therapy.