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1.
Luminescence ; 38(5): 568-575, 2023 May.
Article in English | MEDLINE | ID: mdl-36929687

ABSTRACT

In the current study, α-Bi2 O3 and ß-Bi2 O3 were synthesised using a one-step, novel, solid-solid combustion technique. The reaction rate was increased with the use of microwaves (molecular heating) compared to direct or indirect heating. A strong relationship was observed between the fuel, polymorphic structure, shape and optical properties of the synthesised Bi2 O3 . Photoluminescence studies reveal that two major visible emissions are observed for all samples. The two emissions are distinct with a broad peak in blue and a narrow peak in green. The intensity of the green characteristic emission depends strongly on the heating method used for synthesis and is more intense for microwave-synthesised samples.


Subject(s)
Microwaves
2.
J Clin Exp Hepatol ; 12(6): 1535-1546, 2022.
Article in English | MEDLINE | ID: mdl-36340307

ABSTRACT

Background and aim: Non-alcoholic fatty liver disease (NAFLD) presents with the accumulation of excessive intra-hepatic fat without significant alcohol intake. Multifactorial pathogenesis is reported to be involved. Reduced lysosomal acid lipase (LAL) activity is suggested as one of the novel-involved pathogenic mechanisms. This review summarizes the available evidence on the role of LAL activity in NAFLD pathogenesis. Methods: Four databases namely, PubMed/Medline, Science direct, Cochrane Library, and Google scholar were searched to identify relevant observational records evaluating the role of LAL activity in the pathogenesis of NAFLD. All studies were assessed for their quality by using Newcastle-Ottawa Scale or The Joanna Briggs Institute Critical Appraisal tools for cohort and cross-sectional studies, respectively. The estimates of LAL activity and other clinical outcomes were expressed as mean (SD) and number (%) as presented in the primary studies. Results: A total of nine good quality studies with 1711 patients with NAFLD and 877 controls from different groups (healthy volunteers, alcoholics, cryptogenic cirrhosis, and HCV-positive) were included. From the NAFLD group, 59.55% were males and the overall mean age ranged between the studies from 12.6 ± 8.5 months in pediatrics to 58.90 ± 13.82 years in adults. In the NAFLD group, the LAL activity varied from 0.53 ± 0.08 to 1.3 ± 0.70 (nmol/spot/hr) between the studies which was less than all control groups except cryptogenic cirrhosis patients (0.5 ± 0.15 nmol/spot/hr). Of the other outcomes of interest, ALT, AST, total cholesterol, triglyceride, and LDL cholesterol were found elevated in NAFLD patients than in controls. Conclusion: The current evidence suggests a potential correlation of reduced LAL activity with NAFLD pathogenesis according to its severity. Large-scale studies are recommended, more importantly in patients with NAFLD having no metabolic or genetic involvement. Further LAL can act as a new non-invasive diagnostic biomarker to identify that specific NAFLD subgroup.

3.
Preprint in English | medRxiv | ID: ppmedrxiv-22275149

ABSTRACT

Identification and monitoring of SARS-CoV-2 Variants of Concern/Interest (VOC/VOIs) is essential to guide public health measures. We report the surveillance of VOCs circulating in Karachi during the pandemic between April 2021 and February 2022. We screened 2150 SARS-CoV-2 PCR positive samples received at the AKUH Clinical Laboratories. VOC was identified using a PCR-based approach targeting lineage-specific mutations using commercially available assays. Of the SARS-CoV-2 PCR positive samples, 81.7% had VOC/VOI, while 18.3% were undetermined. Alpha variants were predominant at 82.5% and 40.3% of the cases in April and May 2021. Beta variants increased in May (29%) and June (42%) and then reduced to 6% by July. Gamma variant cases were at 14.5% and 9% in May and June, respectively. Delta variants first detected in May, increased to comprise 66% of all variants by July, remaining dominant in August, September, October, and November 2021 at 88%, 91%, 91% and 85% respectively. Omicron (BA.1) variants emerged in December, rising to 42% of cases with an increase to 81% by January 2022 and then reducing to 45% in February 2022. Delta variant prevalence was coincident with increased hospital admissions and mortality. The Omicron variant surge was associated with increased daily infections but limited COVID-19 severity. We highlight the predominance of the VOCs identified through a rapid PCR based approach. As this is important to inform a public health response, we propose that a mutation targeted approach can be a rapid, lower cost solution to aid tracking of known VOCs during pandemic waves.

4.
Preprint in English | bioRxiv | ID: ppbiorxiv-480826

ABSTRACT

Since the start of COVID-19 pandemic, Pakistan has experienced four waves of pandemic. The fourth wave ended in October, 2021 while the fifth wave of pandemic starts in January, 2022. The data regarding the circulating strains after the fourth wave of pandemic from Pakistan is not available. The current study explore the genomic diversity of SARS-CoV-2 after fourth wave and before fifth wave of pandemic through whole genome sequencing. The results showed the circulation of different strains of SARS-CoV-2 during November-December, 2021. We have Omicron BA.1 (n=4), Lineage A (n=2) and delta AY.27 (n=1) variants of SARS-CoV-2 in the population of Islamabad. All the isolates harbors characteristics mutations of omicron and delta variant in the genome. The lineage A isolate harbors a nine amino acid (68-76) and a ten amino acid (679-688) deletion in the genome. The circulation of omicron in the population before the fifth wave of pandemic and subsequent upsurges of COVID-19 positive cases in Pakistan highlights the importance of genomic surveillance.

5.
Ther Adv Rare Dis ; 2: 26330040211026928, 2021.
Article in English | MEDLINE | ID: mdl-37181111

ABSTRACT

Background: Lysosomal acid lipase deficiency (LAL-D) is a very rare genetic abnormality caused by LIPA gene mutation. The disease has two distinct clinical variants in humans: Wolman disease in infants and cholesteryl ester storage disease in children and adults. Both conditions are characterized by elevated serum transaminases, dyslipidaemia, severe liver steatosis and accelerated fibrosis or cirrhosis, contributing to its high rate of early mortality. Recently sebelipase alfa (recombinant human LAL) was launched to address its underlying pathology. This systematic review evaluates the safety and efficacy of sebelipase alfa for LAL-D. Methods: This systematic review was performed following the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Clinical trial records were systematically searched in PubMed/Medline, ClinicalTrials.gov., Cochrane Library and Google Scholar up to September 2020. Records that have reported at least one of the included outcomes were included. Baseline and endpoint mean and standard deviation (SD) for all outcomes were recorded. For safety, frequency and overall distribution of different adverse events were included. Results: A total of seven records from five individual studies with 110 LAL-D patients were included into this study. The mean age ranged from 2.57 months in infants to 31.6 years among adults. Serum transaminases (alanine aminotransferase and aspartate aminotransferase), serum lipids (total cholesterol, triglycerides, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol), gamma-glutamyl transferase and liver volume were included as efficacy outcomes. Final pooled results were synthesized as a change from baseline to end of the treatment. A significant effect on both serum transaminases and other serum lipid was achieved (p < 0.01), while non-significant differences were seen for GGT and liver volume as p = 0.35 and p = 0.08 was observed. Mostly the adverse events related to the infusions were infrequent and mild-to-moderate in severity. Conclusion: Sebelipase alfa as an enzyme replacement provides an effective, safe and well tolerated treatment in both variants of LAL-D. Plain language summary: A systematic literature review on safety and efficacy of enzyme replacement therapy in lysosomal acid lipase deficiency Lysosomal acid lipase deficiency (LAL-D) is a rare, progressive, genetic disorder caused by functional mutations in the LIPA gene, which encodes LAL enzyme. This enzyme maintains lipid homeostasis by hydrolysing the cholesterol esters and triglycerides. Patients with deficient LAL activity are seen with abnormal liver functions which keep them at a high risk of early mortality. Clinical diagnosis of this disease is very challenging due to both its low prevalence and low awareness among patients/clinicians and additionally due to its overlap with other liver/lipid disorders. Also, owing to lack of safe and effective treatment, dietary modifications and some lipid modifying drugs are usually used to control the LAL-D manifestations. Recently, recombinant human LAL named as sebelipase alfa (Kanuma™, Alexion Pharmaceuticals, Inc., New Haven, Connecticut, USA) was approved in 2015 for the European Union and subsequently in the United States as an enzyme replacement therapy for LAL deficiency. The initial clinical trial data indicate that sebelipase alfa produces a significant improvement in all of the wide range of LAL-D manifestations. However, the cumulative evidence is not reported regarding its safety and effective use. Therefore, a systematic literature review of all the clinical trial records by following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines was undertaken. From all of the available clinical trial records, 110 LAL-D patients treated with sebelipase alfa were included. Serum transaminases, serum lipids, gamma-glutamyl transferase (GGT) and liver volume were included as efficacy outcomes. Final pooled results were synthesized as a change from baseline to end of the treatment. A significant effect on both serum transaminases and other serum lipids was achieved (p < 0.01), while non-significant differences were observed for GGT and liver volume, with p = 0.35 and p = 0.08 respectively. Mostly the adverse events related to the infusions were infrequent and mild-to-moderate in severity. The enzyme replacement provides an effective, safe and well tolerated treatment in both variants of LAL-D.

6.
Trop Anim Health Prod ; 53(1): 14, 2020 Nov 19.
Article in English | MEDLINE | ID: mdl-33211188

ABSTRACT

In the present investigation, differentially expressed genes (DEGs) were studied using RNA sequencing (RNA-seq) technique in porcine peripheral blood mononuclear cells (PBMC) of weaned Ghurrah and crossbred piglets at 3-month age. Transcriptomic analysis was done using three different packages, namely, EBSeq, DESeq2, and edgeR, to identify the DEGs between Ghurrah and crossbred piglets. Total 7717 DEGs were commonly identified by all three packages, out of which 4151 genes found to be up-regulated, and 3566 genes were down-regulated. Functional annotation of these DEGs indicated metabolism as the most commonly enriched category followed by the immune response. Genes related to metabolism and growth were up-regulated in crossbred piglets as compared with Ghurrah piglets, whereas immunity-related genes were up-regulated in Ghurrah piglets elucidating the disease resistance nature of this indigenous breed over crossbred counterparts. Further, eight DEGs, namely, LRP-1, ADCY4, ERRFI1, LDHD, ARG1, OASL, MGARP, and S100A8, were validated by qRT-PCR in a separate set of biological samples and found to be in concordance with RNA-seq results. Finding in the present study provides insight into genes and their molecular mechanisms governing difference in growth performance between Ghurrah and crossbred pigs.


Subject(s)
Disease Resistance/genetics , Gene Expression Profiling/veterinary , Gene Expression , Leukocytes, Mononuclear/metabolism , Sus scrofa/genetics , Animals , India , Sequence Analysis, RNA/veterinary , Sus scrofa/growth & development , Weaning
7.
Preprint in English | medRxiv | ID: ppmedrxiv-20163451

ABSTRACT

Serial household antibody sero-surveys informs the pandemic where testing is non-uniform. Young populations with intergenerational co-residence may have different transmission dynamics. We conducted two serial cross-sectional surveys in April and June 2020 in low- and high-transmission neighborhoods of Karachi, Pakistan, using random sampling. Symptoms were assessed and blood tested for antibody using chemiluminescence. Seroprevalence was adjusted using Bayesian regression and post stratification. CRI with 95% confidence intervals was obtained. We enrolled 2004 participants from 406 households. In June 8.7% (95% CI 5.1-13.1) and 15.1% (95% CI 9.4-21.7) were infected in low- and high-transmission-areas respectively compared with 0.2% (95% CI 0-0.7) and 0.4% (95% CI 0-1.3) in April. Conditional risk of infection was 0.31 (95% CI 0.16-0.47) and 0.41(95% CI 0.28-0.52) respectively with only 5.4% symptomatic. Rapid increase in seroprevalence from baseline is seen in Karachi, with a high probability of infection within household. Article Summary LineRapid increase in seroprevalence of antibodies against SARS-CoV-2 was seen in Karachi, Pakistan from April to June 2020 with a high conditional risk of infection within the household

8.
J Anal Toxicol ; 44(7): 741-746, 2020 Oct 12.
Article in English | MEDLINE | ID: mdl-32591773

ABSTRACT

Neonatal drug exposure is currently assessed using meconium, urine, blood, hair, or umbilical cord tissue/blood. Due to the invasiveness, challenges, and limitations of collection, and/or analytical difficulties of these matrices, oral fluid may be a more desirable matrix in diagnosing opioid exposure and risk for opioid withdrawal in neonatal abstinence syndrome. Traditional oral fluid collection devices are not viable options as they are too large for neonates' mouths and may contain chemicals on the collection pad. Unstimulated and stimulated infant oral fluid samples have been used for therapeutic drug monitoring as an alternative matrix to blood. The objective of this study was to assess the viability of a simple oral fluid collection system using a sterile foam-tipped swab rinsed in phosphate-buffered saline. Two infants were administered fentanyl for post-operative pain relief while hospitalized in the Neonatal Intensive Care Units at the Children's Hospital of Richmond of Virginia Commonwealth University. Oral fluid samples were collected at 16 h, 2 days, and/or 7 days following the start of intravenous infusion of fentanyl. Samples were analyzed by ultra-high-pressure liquid chromatography-tandem mass spectrometry for fentanyl and norfentanyl after solid-phase extraction. In one of the three samples tested, fentanyl and norfentanyl were detected at concentrations of 28 and 78 ng/mL, respectively. Based on the infusion rate, the theoretical oral fluid fentanyl concentration at steady state was calculated to be 33 ng/mL.


Subject(s)
Fentanyl/metabolism , Saliva/metabolism , Forensic Toxicology , Humans , Infant , Infant, Newborn , Solid Phase Extraction
9.
Front Genet ; 11: 589496, 2020.
Article in English | MEDLINE | ID: mdl-33391343

ABSTRACT

Vrindavani is an Indian composite cattle breed developed by crossbreeding taurine dairy breeds with native indicine cattle. The constituent breeds were selected for higher milk production and adaptation to the tropical climate. However, the selection response for production and adaptation traits in the Vrindavani genome is not explored. In this study, we provide the first overview of the selection signatures in the Vrindavani genome. A total of 96 Vrindavani cattle were genotyped using the BovineSNP50 BeadChip and the SNP genotype data of its constituent breeds were collected from a public database. Within-breed selection signatures in Vrindavani were investigated using the integrated haplotype score (iHS). The Vrindavani breed was also compared to each of its parental breeds to discover between-population signatures of selection using two approaches, cross-population extended haplotype homozygosity (XP-EHH) and fixation index (F ST). We identified 11 common regions detected by more than one method harboring genes such as LRP1B, TNNI3K, APOB, CACNA2D1, FAM110B, and SPATA17 associated with production and adaptation. Overall, our results suggested stronger selective pressure on regions responsible for adaptation compared to milk yield.

10.
Diabetes Res Clin Pract ; 154: 90-100, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31238058

ABSTRACT

AIM: This study was aimed to evaluate the cardiomyopathy in patients with type 2 diabetes mellitus (T2DM) who live with or without cardiovascular complications by estimating different cardiac biomarkers. METHODS: This cross-sectional study enrolled 125 participants including 25 healthy volunteers and 100 T2DM patients. After meeting all inclusion criteria, the participants were categorized into five groups (N = 25 in each) as; healthy volunteers (I), T2DM (II), T2DM with hypertension (III), T2DM with dyslipidemia (IV), T2DM with hypertension and dyslipidemia (V). Pearson's correlation analysis was performed to assess the significant association between cardiac biomarkers other biochemical parameters. P-values <0.05 were considered statistically significant. RESULTS: The average age of the participants was found to be 55.04 ±â€¯7.51 years. The positive correlation was found between HbA1c and calcium or BNP levels however, a negative association was observed with zinc level. Group V showed higher mean of BNP (pg/mL) as 86.73 ±â€¯64.49 followed by Group III (61.02 ±â€¯53.69), IV (33.88 ±â€¯33.71), II (13.49 ±â€¯11.67) and I (5.54 ±â€¯1.49) which predicts the subclinical cardiomyopathies in the respective groups. Serum zinc (µg/dL) level were significantly lower in Group V (52.72 ±â€¯12.16) followed by III (56.15 ±â€¯9.64), IV (58.10 ±â€¯10.05), II (59.49 ±â€¯11.33) and I (73.96 ±â€¯21.91). CONCLUSIONS: In summary, BNP and calcium levels were significantly elevated while zinc was significantly reduced in T2DM patients with cardiovascular complication. Results from the study also shown positive correlation between BNP, calcium, Troponin-I levels and blood pressure. However, further longitudinal studies required to confirm these findings.


Subject(s)
Biomarkers/analysis , Cardiomyopathies/diagnosis , Diabetes Mellitus, Type 2/complications , Dyslipidemias/physiopathology , Hypertension/physiopathology , Cardiomyopathies/etiology , Cardiomyopathies/metabolism , Case-Control Studies , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Prognosis
11.
Int J Surg Case Rep ; 53: 50-53, 2018.
Article in English | MEDLINE | ID: mdl-30368126

ABSTRACT

INTRODUCTION: Lipoblastoma usually develops in extremities and trunk during infancy or childhood. Its occurrence in head and neck is rare. CASE PRESENTATION: Here we present a case of lipoblastoma in 14 years old female who developed swelling in the nape of her neck. Initially the diagnosis of lymphangioma was made on the basis MRI findings but histopathology after excisional biopsy confirmed it to be lipoblastoma. CONCLUSION: Lipoblastoma can rarely present as swelling in the nape of neck in adolescents.

12.
Article in English | WPRIM (Western Pacific) | ID: wpr-8647

ABSTRACT

From 2013 to 2015, the National Institute of Health, Pakistan, received 1,270 blood samples of suspected dengue cases reported from inpatient and outpatient departments of various hospitals in Khyber Pakhtunkhwa (KPK) province. In this study, we determined the circulating dengue virus (DENV) serotypes using real-time reverse transcriptase (RT)-PCR to understand the serotype-based epidemiology of DENV. All four serotypes (DENV-1 [6%], DENV-2 [33%], DENV-3 [47%], and DENV-4 [0.1%]) were found circulating during the study period. Our findings suggest the need for an active surveillance system coupled with the laboratory diagnosis, especially in the chronic endemic areas of the country. Public awareness programs are needed for effective control and prevention of outbreaks in the future.


Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , Dengue/diagnosis , Dengue Virus/genetics , Disease Outbreaks , Pakistan/epidemiology , RNA, Viral/genetics , Real-Time Polymerase Chain Reaction , Serogroup
13.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-951430

ABSTRACT

Objective: To high light some epidemiological, clinical and diagnostic features of dengue fever during an outbreak and the role of different diagnostic techniques to achieve the highest level of accuracy in results. Methods: Blood samples (n = 323) were collected along with epidemiological and clinical data from suspected dengue patients who visited different hospitals in Swat and Mansehra district of Pakistan between May-November 2013 during a dengue outbreak. Samples were tested for the detection of viral nucleic acid by real-time PCR, non structural protein-1 (NS1) antigen and IgM antibodies by ELISA. Results: Out of 323 cases with clinical dengue infection, 304 were positive by one or more diagnostic parameter; 201 samples were positive by real-time PCR, 209 were positive by NS1 ELISA and 190 were positive by IgM antibodies. Sensitivities of real-time PCR and NS1 ELISA were comparable for early diagnosis of dengue virus infection, IgM antibody detection assay was found useful for the diagnosis in the samples collected later than day 5 of onset. Conclusions: The use of real-time PCR or detection of non structural protein NS1 by ELISA followed by IgM antibodies detection can be recommended for early diagnosis of dengue virus infection with a high level of accuracy.

14.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-951288

ABSTRACT

Objective To evaluate NS1 antigen detection ELISA for the early laboratory diagnosis of dengue virus infection. Methods The present study was conducted to evaluate the overall positivity of NS1 antigen detection ELISA and its comparison with viral RNA detection via real time PCR and IgM antibodies detection by ELISA. Results A total of 1270 serum samples were tested 86% (1097/1270) were detected positive by one or more than one diagnostic test. Out of 1 270, 64% (807/1270) were positive by NS1 ELISA and 52% (662/1270), 51% (646/1270) were positive by real-time RT-PCR and IgM ELISA respectively. Conclusions NS1 antigen detection ELISA is highly suitable diagnostic tools and it also has great value for use in outbreak and epidemic situation.

15.
Article in English | WPRIM (Western Pacific) | ID: wpr-820257

ABSTRACT

OBJECTIVE@#To high light some epidemiological, clinical and diagnostic features of dengue fever during an outbreak and the role of different diagnostic techniques to achieve the highest level of accuracy in results.@*METHODS@#Blood samples (n = 323) were collected along with epidemiological and clinical data from suspected dengue patients who visited different hospitals in Swat and Mansehra district of Pakistan between May-November 2013 during a dengue outbreak. Samples were tested for the detection of viral nucleic acid by real-time PCR, non structural protein-1 (NS1) antigen and IgM antibodies by ELISA.@*RESULTS@#Out of 323 cases with clinical dengue infection, 304 were positive by one or more diagnostic parameter; 201 samples were positive by real-time PCR, 209 were positive by NS1 ELISA and 190 were positive by IgM antibodies. Sensitivities of real-time PCR and NS1 ELISA were comparable for early diagnosis of dengue virus infection, IgM antibody detection assay was found useful for the diagnosis in the samples collected later than day 5 of onset.@*CONCLUSIONS@#The use of real-time PCR or detection of non structural protein NS1 by ELISA followed by IgM antibodies detection can be recommended for early diagnosis of dengue virus infection with a high level of accuracy.

16.
Article in English | WPRIM (Western Pacific) | ID: wpr-820788

ABSTRACT

OBJECTIVE@#To evaluate NS1 antigen detection ELISA for the early laboratory diagnosis of dengue virus infection.@*METHODS@#The present study was conducted to evaluate the overall positivity of NS1 antigen detection ELISA and its comparison with viral RNA detection via real time PCR and IgM antibodies detection by ELISA.@*RESULTS@#A total of 1270 serum samples were tested 86% (1097/1270) were detected positive by one or more than one diagnostic test. Out of 1 270, 64% (807/1270) were positive by NS1 ELISA and 52% (662/1270), 51% (646/1270) were positive by real-time RT-PCR and IgM ELISA respectively.@*CONCLUSIONS@#NS1 antigen detection ELISA is highly suitable diagnostic tools and it also has great value for use in outbreak and epidemic situation.

17.
PLoS One ; 8(11): e79959, 2013.
Article in English | MEDLINE | ID: mdl-24260327

ABSTRACT

BACKGROUND: There is little information about influenza among the Pakistani population. In order to assess the trends of Influenza-like-Illness (ILI) and to monitor the predominant circulating strains of influenza viruses, a country-wide lab-based surveillance system for ILI and Severe Acute Respiratory Illness (SARI) with weekly sampling and reporting was established in 2008. This system was necessary for early detection of emerging novel influenza subtypes and timely response for influenza prevention and control. METHODS: Five sentinel sites at tertiary care hospitals across Pakistan collected epidemiological data and respiratory samples from Influenza-like illness (ILI) and severe acute respiratory illness (SARI) cases from January 2008 to December 2011. Samples were typed and sub-typed by Real-Time RT-PCR assay. RESULTS: A total of 6258 specimens were analyzed; influenza virus was detected in 1489 (24%) samples, including 1066 (72%) Influenza type A and 423 (28%) influenza type B viruses. Amongst influenza A viruses, 25 (2%) were seasonal A/H1N1, 169 (16%) were A/H3N2 and 872 (82 %) were A(H1N1)pdm09. Influenza B virus circulation was detected throughout the year along with few cases of seasonal A/H1N1 virus during late winter and spring. Influenza A/H3N2 virus circulation was mainly observed during summer months (August-October). CONCLUSIONS: The findings of this study emphasize the need for continuous and comprehensive influenza surveillance. Prospective data from multiple years is needed to predict seasonal trends for vaccine development and to further fortify pandemic preparedness.


Subject(s)
Influenza, Human/epidemiology , Orthomyxoviridae/genetics , Adolescent , Adult , Child , Child, Preschool , Early Diagnosis , Humans , Influenza, Human/prevention & control , Influenza, Human/virology , Middle Aged , Pakistan/epidemiology , Population Surveillance , Seasons , Young Adult
18.
Heart ; 99(7): 491-6, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23406689

ABSTRACT

OBJECTIVE: The Fontan operation is a staged palliation for complex congenital heart disease and single ventricle physiology. Perioperative survivors of the Fontan operation experience long-term cardiac complications, including death. Liver and renal dysfunction are reported in these patients and have a direct effect on morbidity and mortality. This study aims to investigate whether the Model for End-stage Liver Disease eXcluding INR score (function of creatinine and total bilirubin, MELD-XI) predicts risk for cardiac mortality or transplantation in patients with Fontan circulation. DESIGN AND SETTING: Retrospective, single-centre study. Time of first evaluation was the time of the earliest available MELD-XI score measurement, and follow-up was terminated by a cardiac event or by the last clinical evaluation. PATIENTS: Patients surviving after Fontan surgery and evaluated at Boston Children's Hospital between 1993 and 2008. MAIN OUTCOME MEASURE: Composite endpoint of sudden death, death from congestive heart failure or cardiac transplantation. RESULTS: The MELD-XI score was calculated as MELD-XI=11.76(loge creatinine)+5.112(loge total bilirubin)+9.44. Ninety-six patients were included (52 male, median age 26 years). After a mean follow-up period of 5.7 years, 18 patients (19%) experienced the composite end point. Baseline MELD-XI score was independently and directly related to the incidence of the composite endpoint (HR for high MELD-XI score group of 7.76, 95% CI 2.05 to 29.33, p=0.008). CONCLUSIONS: Fontan patients with a higher MELD-XI score have shorter freedom from sudden cardiac death, death from congestive heart failure and cardiac transplantation.


Subject(s)
Death, Sudden, Cardiac/etiology , End Stage Liver Disease/diagnosis , End Stage Liver Disease/mortality , Fontan Procedure/mortality , Heart Defects, Congenital/mortality , Heart Defects, Congenital/surgery , Heart Failure/mortality , Heart Failure/surgery , Heart Transplantation/mortality , Adolescent , Adult , Bilirubin/blood , Biomarkers/blood , Boston , Child , Creatinine/blood , End Stage Liver Disease/blood , End Stage Liver Disease/etiology , Female , Fontan Procedure/adverse effects , Heart Failure/blood , Heart Failure/etiology , Heart Failure/physiopathology , Heart Transplantation/adverse effects , Hemodynamics , Hospitals, Pediatric , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Multivariate Analysis , Proportional Hazards Models , Retrospective Studies , Risk Assessment , Risk Factors , Severity of Illness Index , Time Factors , Treatment Outcome , Young Adult
19.
PLoS One ; 7(8): e41866, 2012.
Article in English | MEDLINE | ID: mdl-22916112

ABSTRACT

BACKGROUND: In early 2009, a novel influenza A(H1N1) virus that emerged in Mexico and United States rapidly disseminated worldwide. The spread of this virus caused considerable morbidity with over 18000 recorded deaths. The new virus was found to be a reassortant containing gene segments from human, avian and swine influenza viruses. METHODS/RESULTS: The first case of human infection with A(H1N1)pdm09 in Pakistan was detected on 18(th) June 2009. Since then, 262 laboratory-confirmed cases have been detected during various outbreaks with 29 deaths (as of 31(st) August 2010). The peak of the epidemic was observed in December with over 51% of total respiratory cases positive for influenza. Representative isolates from Pakistan viruses were sequenced and analyzed antigenically. Sequence analysis of genes coding for surface glycoproteins HA and NA showed high degree of high levels of sequence identity with corresponding genes of regional viruses circulating South East Asia. All tested viruses were sensitive to Oseltamivir in the Neuraminidase Inhibition assays. CONCLUSIONS: Influenza A(H1N1)pdm09 viruses from Pakistan form a homogenous group of viruses. Their HA genes belong to clade 7 and show antigenic profile similar to the vaccine strain A/California/07/2009. These isolates do not show any amino acid changes indicative of high pathogenicity and virulence. It is imperative to continue monitoring of these viruses for identification of potential variants of high virulence or drug resistance.


Subject(s)
Influenza A Virus, H1N1 Subtype/genetics , Influenza, Human/epidemiology , Molecular Epidemiology , Glycosylation , Hemagglutinin Glycoproteins, Influenza Virus/metabolism , Humans , Influenza A Virus, H1N1 Subtype/enzymology , Influenza A Virus, H1N1 Subtype/metabolism , Influenza, Human/virology , Neuraminidase/metabolism , Pakistan/epidemiology , Phylogeny
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