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1.
Saudi Med J ; 43(12): 1390-1396, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36517065

ABSTRACT

OBJECTIVES: To evaluate the demographics, clinical presentation, laboratory data, chest radiographs, and outcomes of pediatric patients with critical coronavirus disease 2019 (COVID-19). METHODS: This retrospective study included 34 children who were diagnosed with severe COVID-19 pneumonia between August 2020 and July 2021. Severe pneumonia was defined as fever, respiratory distress (tachypnea, chest retractions, and hypoxia [oxygen saturation <90% in room air]), and obvious infiltrations on chest radiography. RESULTS: Ages of the patients ranged from newborns to 12 years old, with a median of 24 months (interquartile range: 12-72 months). Preschool-aged children were the most common age group (44%). Levels of inflammatory markers (C-reactive protein, ferritin, and procalcitonin) were elevated in most patients. A total of 13 patients developed severe acute respiratory distress syndrome (ARDS), while 4 developed multiorgan failure. Despite receiving supportive therapy, 2 (5.9%) patients died due to severe septic shock and multiorgan failure. One deceased patient was born prematurely at 30 weeks, while the other had chronic granulomatous disease. CONCLUSION: This study described a single-center cohort of pediatric patients with severe COVID-19 pneumonia. In this cohort, children with cardiopulmonary comorbidities and ARDS had a high mortality and long-term morbidity, as observed in other pediatric studies.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Infant, Newborn , Child, Preschool , Child , Humans , Infant , Retrospective Studies , SARS-CoV-2 , Dyspnea , Radiography
2.
Medicine (Baltimore) ; 100(22): e25919, 2021 Jun 04.
Article in English | MEDLINE | ID: mdl-34087834

ABSTRACT

ABSTRACT: Most of the reports about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children reported mild-to-moderate disease manifestations. However, recent reports explored a rare pediatric multisystem syndrome possibly associated with SARS-CoV-2 infection termed multisystem inflammatory syndrome in children (MIS-C).The study prospectively enrolled 5 patients with clinical and laboratory evidence of MIS-C associated with SARS-CoV-2 infection. They were admitted to the pediatric intensive care unit (PICU). Their clinical presentation, laboratory, and outcome were described.All patients shared similar clinical presentations such as persistent documented fever for more than 3 days, respiratory symptoms, gastrointestinal involvement, and increased inflammatory markers (CRP, ESR, and ferritin). Three patients had concurrent positive coronavirus disease 2019 (COVID-19) infection, and the other 2 patients had contact with suspected COVID-19 positive patients. They were all managed in the PICU and received intravenous immunoglobulin, systemic steroid, and hydroxychloroquine. The hospital stays ranged between 3 and 21 days. One patient died due to severe multiorgan failures and shock, and the other 4 patients were discharged with good conditions.Pediatric patients with SARS-CoV-2 are at risk for MIS-C. MIS-C has a spectrum of clinical and laboratory presentations, and the clinicians need to have a high index of suspicion for the diagnosis and should initiate its early treatment to avoid unfavorable outcomes. Long-term follow-up studies will be required to explore any sequelae of MIS-C, precisely the cardiovascular complications.


Subject(s)
COVID-19/epidemiology , COVID-19/physiopathology , Systemic Inflammatory Response Syndrome/epidemiology , Systemic Inflammatory Response Syndrome/physiopathology , Adrenal Cortex Hormones/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Child , Child, Preschool , Female , Humans , Hydroxychloroquine/therapeutic use , Immunoglobulins/therapeutic use , Inflammation Mediators/metabolism , Intensive Care Units, Pediatric , Length of Stay , Male , Prospective Studies , SARS-CoV-2 , Saudi Arabia/epidemiology , Severity of Illness Index , Systemic Inflammatory Response Syndrome/drug therapy , COVID-19 Drug Treatment
3.
Intervirology ; 62(5-6): 205-209, 2019.
Article in English | MEDLINE | ID: mdl-32208395

ABSTRACT

BACKGROUND: Human cytomegalovirus (HCMV) infection spreads easily by interpersonal contact. OBJECTIVE: This study determined the prevalence of seropositivity of cytomegalovirus immunoglobulin G (IgG) in the Asir Region, Kingdom of Saudi Arabia. METHODS: The study evaluated the seropositivity for cytomegalovirus-specific IgG in 460 females. Collected samples were processed and tested using enzyme-linked immunosorbent assay and specific HCMV IgG. RESULTS: The study showed that all the respondents aged 15-20 years were seropositive for the HCMV. HCMV seropositive status was recorded in 99.2% of the older patients (>40 years of age). In the remaining age groups, the rate of seropositivity ranged from 95.7 (age range 20-25 years) to 98.9% (age range 30 years). CONCLUSIONS: In all age groups of females tested, the prevalence of seropositive for HCMV was high, i.e., in the range of 95.7-100%.

4.
BMC Infect Dis ; 13: 209, 2013 May 08.
Article in English | MEDLINE | ID: mdl-23657114

ABSTRACT

BACKGROUND: Diarrheal diseases represent a major worldwide public health problem particularly in developing countries. Each year, at least four million children under five years of age die from diarrhea. Rotavirus, enteric adenovirus and some bacterial species are the most common identified infectious agents responsible for diarrhea in young children worldwide. This study was conducted to determine prevalence of rotavirus and adenovirus associated with diarrhea among displaced communities in Khartoum state, Sudan. METHODS: A total of seven hundred and ten patients, children and adults, suffering from diarrhea were examined. The clinical history, socio-demographic characteristics, physical examination findings and laboratory investigations were recorded. Stool samples or rectal swabs were collected and tested for rotavirus and adenovirus antigens using the immuno-chromatography test (ICT). Characterization of the identified Rotaviruses, as a major cause of diarrhea, was then made using real time-reverse transcription PCR. To make the study legal, an ethical clearance was obtained from Sudan Ministry of health- Research Ethical Committee. Written consent was taken from adult subjects, and also from children mothers.The participants were informed using simple language about the infection, aim of the research and the benefits of the study. RESULTS: Out of the 710 patients, viral pathogens were detected in only 99 cases (13.9%). Of the 99 cases of viral diarrhea, 83 (83.8%) were due to rotaviruses while 16 (16.2%) attributed to adenovirus. Of the 83 rotaviruses identified, 42 were characterized by RT-PCR, of these 40 (95.2%) were proved as type A (VP6), and 2 (4.8%) type C (VP7). Type C (VP7) rotavirus was detected in samples collected from children under 5 years only. CONCLUSIONS: In conclusion, most cases of viral diarrhea are found to be caused by rotavirus especially among children less than five years. Most of the identified rotavirus belonged to type A (VP6).It was also evident that most patients are those who drank untreated water obtained from donkey carts source and who had no access to latrines, and lived in poor environmental conditions would acquire diarrheal infection.


Subject(s)
Adenoviridae Infections/epidemiology , Adenoviridae Infections/virology , Diarrhea/epidemiology , Diarrhea/virology , Rotavirus Infections/epidemiology , Rotavirus Infections/virology , Adenoviridae/classification , Adenoviridae/genetics , Adenoviridae/isolation & purification , Adolescent , Adult , Child , Child, Preschool , Cross-Sectional Studies , Feces/virology , Humans , Infant , Polymerase Chain Reaction , Prevalence , Refugees/statistics & numerical data , Reverse Transcriptase Polymerase Chain Reaction , Rotavirus/classification , Rotavirus/genetics , Rotavirus/isolation & purification , Socioeconomic Factors , Sudan/epidemiology
5.
J Clin Invest ; 117(12): 3730-41, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18037988

ABSTRACT

The clinical utility of anthracycline anticancer agents, especially doxorubicin, is limited by a progressive toxic cardiomyopathy linked to mitochondrial damage and cardiomyocyte apoptosis. Here we demonstrate that the post-doxorubicin mouse heart fails to upregulate the nuclear program for mitochondrial biogenesis and its associated intrinsic antiapoptosis proteins, leading to severe mitochondrial DNA (mtDNA) depletion, sarcomere destruction, apoptosis, necrosis, and excessive wall stress and fibrosis. Furthermore, we exploited recent evidence that mitochondrial biogenesis is regulated by the CO/heme oxygenase (CO/HO) system to ameliorate doxorubicin cardiomyopathy in mice. We found that the myocardial pathology was averted by periodic CO inhalation, which restored mitochondrial biogenesis and circumvented intrinsic apoptosis through caspase-3 and apoptosis-inducing factor. Moreover, CO simultaneously reversed doxorubicin-induced loss of DNA binding by GATA-4 and restored critical sarcomeric proteins. In isolated rat cardiac cells, HO-1 enzyme overexpression prevented doxorubicin-induced mtDNA depletion and apoptosis via activation of Akt1/PKB and guanylate cyclase, while HO-1 gene silencing exacerbated doxorubicin-induced mtDNA depletion and apoptosis. Thus doxorubicin disrupts cardiac mitochondrial biogenesis, which promotes intrinsic apoptosis, while CO/HO promotes mitochondrial biogenesis and opposes apoptosis, forestalling fibrosis and cardiomyopathy. These findings imply that the therapeutic index of anthracycline cancer chemotherapeutics can be improved by the protection of cardiac mitochondrial biogenesis.


Subject(s)
Antibiotics, Antineoplastic/adverse effects , Antimetabolites/pharmacology , Carbon Monoxide/pharmacology , Cardiomyopathies/enzymology , Doxorubicin/adverse effects , Heme Oxygenase (Decyclizing)/metabolism , Mitochondria, Heart/enzymology , 3-Phosphoinositide-Dependent Protein Kinases , Animals , Antibiotics, Antineoplastic/pharmacology , Apoptosis/drug effects , Apoptosis/genetics , Cardiomyopathies/chemically induced , Cardiomyopathies/genetics , Cardiomyopathies/pathology , Caspase 3/biosynthesis , Caspase 3/genetics , Cells, Cultured , DNA, Mitochondrial/genetics , DNA, Mitochondrial/metabolism , Doxorubicin/pharmacology , Fibrosis , GATA4 Transcription Factor/genetics , GATA4 Transcription Factor/metabolism , Gene Silencing , Guanylate Cyclase/genetics , Guanylate Cyclase/metabolism , Heme Oxygenase (Decyclizing)/genetics , Male , Mice , Mitochondria, Heart/genetics , Mitochondria, Heart/pathology , Myocardium/enzymology , Myocardium/pathology , Necrosis/chemically induced , Necrosis/enzymology , Necrosis/genetics , Necrosis/pathology , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Rats , Sarcomeres/enzymology , Sarcomeres/genetics , Sarcomeres/pathology
6.
Am J Respir Crit Care Med ; 176(8): 768-77, 2007 Oct 15.
Article in English | MEDLINE | ID: mdl-17600279

ABSTRACT

RATIONALE: The extent, timing, and significance of mitochondrial injury and recovery in bacterial sepsis are poorly characterized, although oxidative and nitrosative mitochondrial damage have been implicated in the development of organ failure. OBJECTIVES: To define the relationships between mitochondrial biogenesis, oxidative metabolism, and recovery from Staphylococcus aureus sepsis. METHODS: We developed a murine model of fibrin clot peritonitis, using S. aureus. The model yielded dose-dependent decreases in survival and resting energy expenditure, allowing us to study recovery from sublethal sepsis. MEASUREMENTS AND MAIN RESULTS: Peritonitis caused by 10(6) colony-forming units of S. aureus induced a low tumor necrosis factor-alpha state and minimal hepatic cell death, but activated prosurvival protein kinase A, B, and C sequentially over 3 days. Basal metabolism by indirect calorimetry was depressed because of selective mitochondrial oxidative stress and subsequent loss of mitochondrial DNA copy number. During recovery, mitochondrial biogenesis was strongly activated by regulated expression of the requisite nuclear respiratory factors 1 and 2 and the coactivator peroxisome proliferator-activated receptor gamma coactivator-1alpha, as well as by repression of the biogenesis suppressor nuclear receptor interacting protein-140. Biogenesis reconstituted mitochondrial DNA copy number and transcription, and restored basal metabolism without significant hepatocellular proliferation. These events dramatically increased hepatic mitochondrial density in transgenic mice expressing mitochondrially targeted green fluorescent protein. CONCLUSIONS: This is the first demonstration that mitochondrial biogenesis restores oxidative metabolism in bacterial sepsis and is therefore an early and important prosurvival factor.


Subject(s)
Mitochondria/metabolism , Sepsis/microbiology , Staphylococcus aureus/pathogenicity , Adaptor Proteins, Signal Transducing/metabolism , Animals , Basal Metabolism , Disease Models, Animal , GA-Binding Protein Transcription Factor/metabolism , Hepatocytes/pathology , Liver/pathology , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Nuclear Proteins/metabolism , Nuclear Receptor Interacting Protein 1 , Nuclear Respiratory Factor 1/metabolism , Oxidative Stress , Peritonitis/microbiology , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , Protein Kinases/biosynthesis , RNA, Messenger/metabolism , Trans-Activators/metabolism , Transcription Factors
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