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1.
Acta Gastroenterol Belg ; 82(2): 261-266, 2019.
Article in English | MEDLINE | ID: mdl-31314186

ABSTRACT

BACKGROUND AND AIMS: The microbiological characteristics of spontaneous bacterial peritonitis (SBP) are changing worldwide with a shift in patterns of SBP and increasing prevalence of antibiotic-resistant bacteria. We, therefore, conducted this retrospective study aiming to characterise the current patterns and microbiology of SBP in our region. METHODS: We performed a retrospective chart review of patients presenting with their first episodes of SBP. The demographical, clinical and laboratory parameters of all patients at first paracentesis were recorded. RESULTS: The study included 200 cirrhotic patients with SBP. Mean age was 60.4±13.5 years and 116 (58%) patients were males. Liver cirrhosis was predominantly viral in 138 (69%) patients. Ascitic fluid cultures were positive in 103 (51.5%) patients and negative in 97 (48.5%). Ninety-eight (95.1%) patients had monomicrobial bacterial growth. The most common variants of spontaneous ascitic fluid infection were culture negative neutrocytic ascites (CNNA) in 97(48.5%) patients and SBP in 65 (32.5%) patients. E.Coli was most frequently isolated microorganism in 41 (39.8%) patients followed by staphylococcus species in 19 (18.4%) patients, Klebsiella pneumonae in 14(13.6%) patients and streptococcus species in 13 (10.7%) patients. The prevalence of extended spectrum beta-lactamases (ESBL) resistant E.Coli was 29.3%. Antibiotic resistance rate for meropenem, piperacillin\ tazobactam, ceftriaxone and ciprofloxacin was 0%, 22.0%, 29.0%, and 28.6% respectively. CONCLUSIONS: Changes in the patterns and microbiology of SBP are evident in our region with increasing prevalence of culture negative SBP, extended spectrum beta-lactamases resistant E.Coli, and increased resistance rate to first line antibiotics. Our data argue for relying on periodic hospital based antibiotic susceptibility data whenever SBP is treated.


Subject(s)
Ascites/microbiology , Ascitic Fluid/microbiology , Bacterial Infections/microbiology , Liver Cirrhosis/microbiology , Liver Cirrhosis/virology , Peritonitis/microbiology , Aged , Bacterial Infections/diagnosis , Humans , Male , Middle Aged , Peritonitis/diagnosis , Retrospective Studies
2.
Rev Sci Tech ; 37(3): 985-997, 2018 12.
Article in English | MEDLINE | ID: mdl-30964454

ABSTRACT

A cross-sectional study was conducted in five regions in Saudi Arabia to investigate the epidemiology of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in dromedary camels (Camelus dromedarius) during April and May2015. Serum and nasal swab samples were tested for MERS-CoV antibodies andribonucleic acid (RNA) using a recombinant enzyme-linked immunosorbent assay (rELISA) and real-time reverse-transcription polymerase chain reaction (rRT-PCR), respectively. The overall MERS-CoV antibody seroprevalence was 80.5%, whereas the overall viral RNA prevalence was 2.4%. The associations of risk factors with each prevalence were quantified using univariate and multivariate analyses. The multivariate models identified region, age, grazing system, exposure to wild animals and dung removal as factors significantly associated with seroprevalence (p ??0.05). A higher seroprevalence was more likely to occur in camels from the Riyadh, Eastern, Northern and Makkah regions than those from the Jazan region; camels ??4 and 1-3 years of age (marginally significant) than calves < 1 year; and camels raised in zero grazing and semi-open grazing systems than those raised in an open grazing system. However, the presence of wild animals and daily dung removal were negatively associated with seroprevalence. On the other hand, region and sex were significantly associated with MERS-CoV RNA prevalence(p ??0.05). A higher viral RNA prevalence was more likely to occur in camels from the Riyadh region and Eastern region (marginally significant) than in those from the Makkah region, and in male camels than female camels. In conclusion, the risk factors identified in this study can be considered to be predictors of MERS-CoV infection in camels and should be taken into account when developing an efficient and cost-effective control strategy.


Une étude transversale a été réalisée au cours des mois d'avril et de mai 2015 dans cinq régions d'Arabie saoudite afin d'élucider l'épidémiologie de l'infection par le coronavirus responsable du syndrome respiratoire du Moyen-Orient(MERS­CoV) chez les dromadaires (Camelus dromedarius). Des échantillons de sérum et des écouvillons nasaux prélevés de dromadaires ont été analysés afin de détecter la présence d'anticorps dirigés contre le MERS-CoV ou d'ARN de ce même virus, en utilisant respectivement une épreuve immuno-enzymatique recombinante (ELISAr) et une amplification en chaîne par polymérase couplée à une transcription inverse (PCR­RT) en temps réel. La prévalence sérologique globale des anticorps dirigés contre le MERS-CoV s'élevait à 80,5 %, tandis que la prévalence globale de l'ARN viral était de 2,4 %. Les corrélations entre les facteurs de risque et les prévalences obtenues ont été quantifiées au moyen d'analyses à une seule et à plusieurs variables. Les modèles à plusieurs variables ont fait apparaître une association significative (p ??0,05) entre la prévalence sérologique et les facteurs suivants : la région, l'âge des animaux, le système pastoral pratiqué, l'exposition à la faune sauvage et l'élimination du fumier. La probabilité d'une forte prévalence sérologique était plus élevée chez les dromadaires provenant des régions de Riyad, de l'Est, du Nord et de la Mecque que chez ceux de la région de Jizan ; chez les dromadaires âgés de plus de quatre ans, ou âgés d'un à trois ans (différence marginalement significative) plutôt que chez les jeunes de moins d'un an ; et enfin chez les dromadaires nourris en stabulation (zéro pâturage) ou en pâturage semi-ouvert plutôt que chez ceux nourris dans des systèmes de pâturage ouvert. En revanche, une corrélation négative a été constatée entre la prévalence sérologique d'une part et la présence d'animaux sauvages et/ou l'élimination quotidienne du fumier, d'autre part. En ce qui concerne la détection virale, une corrélation significative (p ??0,05) a été constatée entre la région et le sexe des animaux et la prévalence de l'ARN du MERS-CoV. La probabilité d'une prévalence plus élevée de l'ARN viral était plus prononcée chez les dromadaires des régions de Riyad et de l'Est (différence marginalement significative) que chez ceux de la région de La Mecque, et chez les mâles que chez les chamelles. En conclusion, les facteurs de risque identifiés dans cette étude peuvent servir d'annonciateurs de l'infection par le MERS-CoV chez les dromadaires et devraient être pris en compte pour élaborer une stratégie efficace et rentable de lutte contre cette maladie.


Los autores describen un estudio transversal efectuado en abril y mayo de 2015 en cinco regiones de Arabia Saudí con objeto de investigar la epidemiologia de la infección de dromedarios (Camelus dromedarius) por el coronavirus del síndrome respiratorio de Oriente Medio (MERS­CoV). A tal efecto se analizaron muestras de suero y exudado nasal para detectar en ellas anticuerpos contra el MERS­CoV y ácido ribonucleico (ARN) del virus, empleando para ello, respectivamente, una técnica de ensayo inmunoenzimático recombinante (ELISAr) y una de reacción en cadena de la polimerasa acoplada a transcripción inversa en tiempo real (rRT­PCR, por sus siglas en inglés). Se calculó que la seroprevalencia global de anticuerpos contra el virus era del 80,5% y que la prevalencia global de ARN vírico era del 2,4%. Utilizando análisis multifactoriales y de una sola variable se cuantificó también la correlación de cada una de esas prevalencias con una serie de factores de riesgo. Con los modelos multifactoriales se observó que la región, la edad, el régimen de pastoreo, la exposición a animales salvajes y la retirada de estiércol eran factores que presentaban una asociación significativa con la seroprevalencia (p ??0,05): era más probable encontrar niveles elevados de seroprevalencia en dromedarios de las regiones de Riad y La Meca y las regiones oriental y septentrional del país que en los de la región de Jizán; en los de 4 o más años y entre 1 y 3 años de edad (correlación ligeramente significativa) que en las crías menores de 1 año; y en los animales estabulados o criados en sistemas de pasto semiabierto que en los criados con regímenes de pasto al aire libre. La presencia de animales salvajes y la retirada cotidiana del estiércol, por su parte, presentaban una correlación negativa con la seroprevalencia. Por otro lado, los factores asociados significativamente con la prevalencia de ARN vírico (p ??0,05) eran la región y el sexo: había mayor probabilidad de encontrar niveles elevados de prevalencia de ARN vírico en dromedarios de la región de Riad y la región oriental (correlación ligeramente significativa) que en los de la región de La Meca, y en machos más que en hembras. En conclusión, los factores de riesgo detectados con este estudio pueden ser considerados predictivos de la infección de dromedarios por el MERS­CoV y deben ser tenidos en cuenta para elaborar una estrategia de lucha que ofrezca a la vez eficacia y rentabilidad.


Subject(s)
Coronavirus Infections , Middle East Respiratory Syndrome Coronavirus , Animals , Camelus , Coronavirus Infections/veterinary , Cross-Sectional Studies , Female , Male , Saudi Arabia , Seroepidemiologic Studies
3.
Clin Exp Immunol ; 191(3): 279-287, 2018 03.
Article in English | MEDLINE | ID: mdl-29277898

ABSTRACT

Acute lung injury (ALI) is a heterogeneous disease with the hallmarks of alveolar capillary membrane injury, increased pulmonary oedema and pulmonary inflammation. The most common direct aetiological factor for ALI is usually parenchymal lung infection or haemorrhage. Reactive oxygen species (ROS) generated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX2) are thought to play an important role in the pathophysiology of ALI. Glucose-6-phosphate dehydrogenase (G6PD) plays an important role both in production of ROS as well as their removal through the supply of NADPH. However, how G6PD modulation affects NOX2-mediated ROS in the airway epithelial cells (AECs) during acute lung injury has not been explored previously. Therefore, we investigated the effect of G6PD inhibitor, 6-aminonicotinamide on G6PD activity, NOX2 expression, ROS production and enzymatic anti-oxidants in AECs in a mouse model of ALI induced by lipopolysaccharide (LPS). ALI led to increased G6PD activity in the AECs with concomitant elevation of NOX2, ROS, SOD1 and nitrotyrosine. G6PD inhibitor led to reduction of LPS-induced airway inflammation, bronchoalveolar lavage fluid protein concentration as well as NOX2-derived ROS and subsequent oxidative stress. Conversely, ALI led to decreased glutathione reductase activity in AECs, which was normalized by G6PD inhibitor. These data show that activation of G6PD is associated with enhancement of oxidative inflammation in during ALI. Therefore, inhibition of G6PD might be a beneficial strategy during ALI to limit oxidative damage and ameliorate airway inflammation.


Subject(s)
Acute Lung Injury/metabolism , Glucosephosphate Dehydrogenase/metabolism , NADPH Oxidases/metabolism , Reactive Oxygen Species/metabolism , Respiratory Mucosa/metabolism , Acute Lung Injury/chemically induced , Acute Lung Injury/drug therapy , Animals , Cells, Cultured , Disease Models, Animal , Flow Cytometry , Gene Expression Regulation , Glucosephosphate Dehydrogenase/antagonists & inhibitors , Humans , Lipopolysaccharides/immunology , Male , Mice , Mice, Inbred BALB C , NADPH Oxidases/genetics , Niacinamide/administration & dosage , Niacinamide/analogs & derivatives , Niacinamide/pharmacology , Oxidative Stress , Respiratory Mucosa/pathology
5.
World J Urol ; 32(5): 1205-11, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24166288

ABSTRACT

PURPOSE: To examine the significance of 90 biomarkers for predicting metastatic status in non-seminomatous germ cell tumors (NSGCT). By predicting metastatic status, it may be possible to eliminate unnecessary therapeutic or diagnostic efforts. MATERIALS AND METHODS: We investigated 552 males who were diagnosed with non-metastatic (n = 273) and metastatic (n = 279) NSGCT between 2000 and 2011. The sample included cancers of different histologies: embryonal cell carcinoma (n = 131), teratoma (n = 55), and mixed histology (n = 366). We collected and analyzed more than 90 parameters via logistic regression: demographic characteristics, medical history, histopathological parameters, and levels of tumor markers and hormones. RESULTS: Testis histology (p = 0.004), clinical symptoms (p = 0.0005), tumor length (p = 0.005), infiltration of the rete testis (p = 0.008), invasion of lymphatic (pL1) and blood vessels (pV1) (p < 0.0001), and levels of enzymes such as LDH, ßHCG, AFP, and FSH (p values as small as <0.0001) were associated with metastatic status. With one model, we identified 14 out of 76 (18.4 %) metastatic NSGCT cases with 93-100 % certainty (positive predictive value) at 99 % specificity by the peripheral blood levels of LDH (day of operation) in combination with FSH measurements (1 day after operation). A second model included pV, tumor length, and FSH (1 day after operation). It identified 25 out of 90 (27.8 %) non-metastatic NSGCT with approximately 90 % certainty (negative predictive value) at 94-98 % sensitivity. CONCLUSIONS: No single parameter was able to discriminate metastatic from non-metastatic NSGCT, but combinations of parameters in two predictive models accurately identified the metastatic status in 23 % of the cases in our sample.


Subject(s)
Models, Statistical , Neoplasms, Germ Cell and Embryonal/secondary , Testicular Neoplasms/pathology , Humans , Male , Neoplasms, Germ Cell and Embryonal/epidemiology , Prognosis , Retrospective Studies , Risk Assessment
6.
Mutagenesis ; 29(1): 55-62, 2014 01 01.
Article in English | MEDLINE | ID: mdl-24342934

ABSTRACT

Although chloroacetonitrile (CAN), a disinfection by-product of chlorination of drinking water, is considered a rodent carcinogen that induces lung adenomas in mice, previous studies on its genotoxicity have yielded inconclusive results. Thus, its cancer mode of action has not been clearly defined. We evaluated CAN-induced genotoxicity in mice using mouse bone marrow micronucleus test, comet assays and expression of genes associated with DNA damage repair. Mice exposed to CAN at 8.75, 17.5, 35 and 52.5mg/kg for 7 days did not exhibit any significant increases in the incidence of micronuclei formation at 24 and 48h after last exposure. However, CAN caused significant suppressions of erythroblast proliferation at the highest dose. In the alkaline comet assay, there was a significant increase in the incidence of DNA strand breaks in mice killed after 3h of last treatment with 35 and 52.5mg/kg/day CAN, while no significant difference in the DNA strand breaks was found in mice killed after 24h of the last treatment. However, slight (but significant) CAN-induced oxidative DNA damage was detected following Fpg digestion at 3-h sampling time, digestion with EndoIII resulted in considerable increases in oxidative DNA damage at 3 and 24h after the last exposure to 35 and 52.5mg/kg/day CAN as detected by oxidative comet assays. The expression of DNA repair genes OGG1 , Apex1, PARP1 and p53 were up-regulated in mice given 35mg/kg/day CAN at 3h but not in 24h after the last treatment except OGG1 . However, the significant up-regulation of OGG1 at 24h after the last treatment further indicates the occurrence of oxidative DNA damage. Overall, CAN exposure is associated with up-regulation of DNA repair gene expression and the induction of oxidative DNA damage, which may be at least partially responsible for CAN-induced genotoxicity and eventually cause carcinogenicity.

7.
J Urol ; 190(3): 1046-51, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23583226

ABSTRACT

PURPOSE: We screened 90 potential parameters as biomarkers of metastatic seminoma to facilitate detection and eliminate unnecessary therapeutic or diagnostic efforts. MATERIALS AND METHODS: A total of 527 men with pure seminoma (diagnosed 2000 to 2011) were followed during therapy. More than 90 demographic/anamnestic (eg age, height, weight) histopathological parameters (testicular/tumor size, testicular intraepithelial neoplasia) and levels of tumor markers (eg α-fetoprotein, ß-human chorionic gonadotropin, lactate dehydrogenase) in peripheral blood and testicular vein were collected for analysis via logistic regression. Previously described risk factors (tumors larger than 4 cm, infiltration of rete testis) were assessed separately. RESULTS: Established parameters such as tumor length (p = 0.0003), involvement of lymphatic (p <0.0001) or vascular channels (p = 0.0009), extent of primary tumor (p <0.0001) and infiltration of the tunica albuginea (p = 0.02) as well as new biomarkers such as absence of testicular intraepithelial neoplasia in tumor bearing testis (p = 0.03), testicular volume (p = 0.04) and tumor volume (p = 0.02) showed a significant association with metastatic disease. This association was also true of lactate dehydrogenase, human chorionic gonadotropin and α-fetoprotein (p <0.0001 at maximum). However, the discriminatory capacity of these biomarkers (concordance or ROC area) did not exceed 65% when examined alone or in combination, and higher values (up to 80%) were detected for enzyme levels. A subset of metastatic seminoma (2% to 27%) was detectable with high accuracy (positive predictive value 92% to 100%) based on enzyme measurements (p <0.0006). CONCLUSIONS: New biomarkers of metastatic seminoma were identified and previously described risk factors were validated. Further prospective studies of these novel parameters are warranted to verify our findings and to explore a potential use for detecting occult metastases.


Subject(s)
Biomarkers, Tumor/blood , Chorionic Gonadotropin, beta Subunit, Human/blood , Seminoma/secondary , Testicular Neoplasms/pathology , alpha-Fetoproteins/metabolism , Adult , Cohort Studies , Combined Modality Therapy/methods , Confidence Intervals , Follow-Up Studies , Humans , Immunohistochemistry , L-Lactate Dehydrogenase/blood , Male , Middle Aged , Multivariate Analysis , Neoplasm Invasiveness/pathology , Neoplasm Metastasis , Neoplasm Staging , Odds Ratio , Predictive Value of Tests , Retrospective Studies , Risk Assessment , Seminoma/blood , Seminoma/therapy , Testicular Neoplasms/blood , Testicular Neoplasms/therapy , Treatment Outcome , Tumor Burden
8.
Radiat Res ; 173(4): 505-11, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20334523

ABSTRACT

Genetic predictive biomarkers of radiosensitivity are being sought to individualize radiation treatment of cancer patients. In this pilot case-control study, we tested the association between TGFB1 T869C codon 10 Leu/Pro (rs1982073), XRCC1 G28152A codon 399 Arg/Gln (rs25487), and XRCC3 C18067T codon 241 Thr/Met (rs861539) single-nucleotide polymorphisms (SNPs) and late reaction to radiotherapy in 60 nasopharyngeal cancer patients. Subcutaneous and deep tissue fibrosis was scored using the RTOG/EORTC grading system. Patients with moderate to severe fibrosis (radiosensitive cases, G2-3, n = 30) were matched and compared to those with little or no reaction (controls, G0-1, n = 30). The three nonsynonymous SNPs were genotyped by direct DNA sequencing. Significant association was observed for TGFB1 T869C and XRCC1 G28152A genotypes (P < or = 0.05). Both variant alleles, TGFB1 869C and XRCC1 28152A, were associated with a lower grade of fibrosis (odds ratios were 0.41, 95% CI: 0.20-0.86, P = 0.02 and 0.30, 95% CI: 0.10-0.89, P = 0.02, respectively), and therefore the wild-types were the risk alleles. Interestingly, there was a significant difference in the median number of risk alleles between the radiosensitive and the control groups (P = 0.006). We conclude that radiotherapy complications are associated with genetic variations in our nasopharynx cancer patients. Our findings support the assumption of the combined effects of multiple SNPs. Large-scale studies are required to confirm these findings before polymorphisms can be used as predictive markers to individualize radiation therapy on genetic bases.


Subject(s)
DNA-Binding Proteins/genetics , Nasopharyngeal Neoplasms/genetics , Nasopharyngeal Neoplasms/radiotherapy , Polymorphism, Single Nucleotide/genetics , Radiation Pneumonitis/etiology , Radiation Pneumonitis/genetics , Radiotherapy, Conformal/adverse effects , Transforming Growth Factor beta1/genetics , Adolescent , Adult , Aged , Biomarkers, Tumor/genetics , Female , Genetic Predisposition to Disease/genetics , Humans , Male , Middle Aged , Nasopharyngeal Neoplasms/complications , Retrospective Studies , Treatment Outcome , X-ray Repair Cross Complementing Protein 1 , Young Adult
9.
Radiat Res ; 167(5): 535-40, 2007 May.
Article in English | MEDLINE | ID: mdl-17474797

ABSTRACT

Inherent radiosensitivity varies widely between individuals. We hypothesized that amino acid substitution variants in two highly radiation-responsive proteins, TP53 (p53) and CDKN1A (p21, Waf1, Cip1), are associated with and could explain individual variations in radiosensitivity. The two non-synonymous single-nucleotide polymorphisms (SNPs) TP53 codon 72 Arg/Pro G>C and CDKN1A codon 31 Ser/Arg C>A were genotyped in 92 normal fibroblast cell strains of different radiosensitivity. The clonogenic surviving fraction at 2 Gy (SF2) ranged between 0.15 and 0.50 (mean = 0.34, SD = 0.08). The mean SF2 was used to divide the cell strains into radiosensitive (45) and normal groups (47). A significant association was observed between SF2 and the TP53 codon 72 haplotype (C compared to G, P = 0.01). No association was observed between CDKN1A codon 31 haplotype and radiosensitivity (P = 0.86). The variant TP53 Arg72 allele was associated with a decrease in radiosensitivity, presumably due to suboptimal function leading to less stringent control of cell division. We conclude that certain SNPs in susceptible genes can influence cellular radiation response. Such risk alleles could ultimately be used as predictive markers for radiosensitivity to help stratifying individuals during assessment of risk of radiation exposure.


Subject(s)
Codon/genetics , Polymorphism, Single Nucleotide/genetics , Polymorphism, Single Nucleotide/radiation effects , Radiation Tolerance/genetics , Tumor Suppressor Protein p53/genetics , Adolescent , Adult , Aged , Alleles , Cell Survival/radiation effects , Cells, Cultured , Child , Female , Fibroblasts/radiation effects , Genotype , Humans , Male , Middle Aged
10.
Radiat Res ; 167(1): 58-65, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17214516

ABSTRACT

We tested the hypothesis that individual variations in the induction of the TP53 tumor suppressor protein by radiation are related to inherent radiosensitivity. Thirty-two fibroblast cell strains were examined. Radiosensitivity was measured by a clonogenic survival assay. The induction of TP53 and its transcriptionally activated CDKN1A (p21) protein were studied by Western blotting 3 h after a single dose of 5 Gy. The relative cell culture age, as determined by the colony size distribution, was studied as a confounding factor. Survival curves showed wide range of radiosensitivity. The surviving fraction at 2 Gy (SF2) ranged between 0.02 and 0.49 (mean = 0.29, SD = 0.13). TP53 induction ranged between 1.28 and 2.34 (mean = 1.80, SD = 0.31). CDKN1A showed a wider induction (1.09-4.05, mean = 2.33, SD = 0.78). Positive correlations were observed between SF2 and TP53 induction (R(2) = 0.62, P < 0.001) and CDKN1A (R(2) = 0.64, P < 0.001). No correlation with the colony size distribution was observed. In conclusion, these results suggest that the individual variations in radiosensitivity and in the level of induction of TP53 (and consequently CDKN1A) are congruent, irrespective of the genetic background of these nontransformed fibroblasts. It is postulated that underlying mechanisms culminating in a stronger TP53 induction lead to higher survival, presumably due to more efficient repair of radiation-induced damage.


Subject(s)
Cyclin-Dependent Kinase Inhibitor p21/genetics , Gene Expression Regulation, Neoplastic , Radiation Tolerance , Tumor Suppressor Protein p53/genetics , Blotting, Western , Cell Culture Techniques/methods , Cyclin-Dependent Kinase Inhibitor p21/biosynthesis , Dose-Response Relationship, Radiation , Fibroblasts/drug effects , Fibroblasts/metabolism , Fibroblasts/radiation effects , Humans , Neoplasms/genetics , Neoplasms/metabolism , Radiation , Temperature , Time Factors , Tumor Cells, Cultured , Tumor Suppressor Protein p53/biosynthesis
11.
Radiat Res ; 161(2): 185-92, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14731071

ABSTRACT

It has been reported that the loss of function of Trp53 protein is associated with a reduction in the expression of radiation-induced potentially lethal damage (PLD). These studies, however, were carried out using either transformed or transfected cell lines, and other factors may have existed that could interfere with PLD repair. In this study, we used isogenic fibroblasts derived from Trp53 knockout mice to study radiation sensitivity, PLD repair, and repair of DNA double-strand breaks (DSBs). Experiments were carried out using wild-type (Trp53(+/+)), heterozygous (Trp53(+/-)) and homozygous mutant (Trp53(-/-)) cells. This is an ideal system because the only difference in the three cell strains is the status of the Trp53 protein. DSB repair was measured by pulsed-field-gel electrophoresis (PFGE), while radiosensitivity and PLD repair were studied using the clonogenic survival assay. Cells were irradiated in plateau phase and then trypsinized and plated either immediately or 24 h later to allow for PLD repair. The results of Western blot analyses showed that Trp53(-/-) cells expressed a putative mutant form of Trp53 that was unable to transcriptionally activate Cdkn1a (p21) protein in response to irradiation. The Trp53(-/-) cells were significantly more radioresistant than the Trp53(+/+) cells, and this was associated with a moderate reduction in PLD repair. DNA repair experiments showed no difference in DSB rejoining capability between the two cell lines. In conclusion, our results show that loss of wild-type Trp53 leads to increased radioresistance with consequent reduction in PLD repair but with no effect on DNA DSB repair.


Subject(s)
DNA Damage , DNA Repair/radiation effects , Fibroblasts/metabolism , Fibroblasts/radiation effects , Gene Expression Regulation/radiation effects , Tumor Suppressor Protein p53/metabolism , Animals , Cell Line , Cell Survival/radiation effects , Dose-Response Relationship, Radiation , Fibroblasts/cytology , Mice , Radiation Tolerance/physiology , Tumor Suppressor Protein p53/deficiency
12.
J Invasive Cardiol ; 12(8): 402-6, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10953103

ABSTRACT

OBJECTIVE: To evaluate the role of balloon coarctation angioplasty (BCA) in the management of patients with native coarctation of the aorta. BACKGROUND: BCA has emerged as an alternative to surgery for patients with native coarctation of the aorta. However, its role remains controversial. METHODS: Over a 7-year period, 103 patients undergoing BCA were enrolled in the study. Hemodynamic evaluation was obtained at baseline and immediately following BCA; 75% of patients returned for follow-up evaluation at 26 +/- 20 months. RESULTS: The systolic gradient across the coarcted segment decreased from 59 +/- 18 mmHg to 10 +/- 11 mmHg following BCA (p < 0.001). The procedure was successful in 82% of patients, and partial improvement was obtained in 17%. Repeat intervention was performed in 13% of the follow-up group. Surgical intervention was needed in 8 patients. CONCLUSION: Balloon angioplasty is an effective first-line intervention in patients with native coarctation of the aorta.


Subject(s)
Angioplasty, Balloon , Aortic Coarctation/therapy , Adolescent , Adult , Aortic Coarctation/diagnostic imaging , Aortic Coarctation/physiopathology , Aortography , Child , Child, Preschool , Female , Follow-Up Studies , Hemodynamics , Humans , Infant , Infant, Newborn , Male , Recurrence , Retrospective Studies
13.
J Clin Periodontol ; 27(2): 93-8, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10703653

ABSTRACT

BACKGROUND: The Hunter TPS Vivacare periodontal probe was invented to perform consistent, accurate and reliable periodontal examinations "with controlled pressures". AIMS: The aims of the present investigation are 3: (1) what is the accuracy of the probing force when various probe heads are used in a correct operation position; (2) what is the effect of over- and under-reading of the operation position on the probing force; (3) what is the accuracy of the probing force when different probe handles are used. The Hunter TPS probe consists of a tip connected to a special spring mechanism, which controls the pressure extended to the probe tip. According to the manufacturer, the force indicator lines coincide at approximately 20 g force. METHOD: The test apparatus consisted of an electronic balance, and an electronic caliper. 12 TPS probes tips and 3 handles were selected to test whether there were differences in force between probes. Each probe tip was adapted to the same handle and tested 10 times. In a 2nd test, the TPS handles and over-, accurate-, and under-readings were analyzed as to how they affect the probing force. The 12 TPS probe tips were connected to each of the 3 handles and tested 10x for each of 3 handles and levels. RESULTS: The range in force between TPS probe tips was 8.4 g (p<0.001). For the handles as well as for each of the readings of the operating positions, the differences were small and non-significant. However, between over- and under-readings, there were statistical significant differences. CONCLUSION: The conclusion is that the variation in force between probe tips is high and always above the manufacturer's "approximately" 20 g. As long as the same handle and the same probe tip are used together, and the examiner is reading the markings correct, the TPS probe is adequate.


Subject(s)
Periodontal Pocket/classification , Periodontics/instrumentation , Electronics, Medical/instrumentation , Electronics, Medical/statistics & numerical data , Equipment Design/statistics & numerical data , Evaluation Studies as Topic , Humans , Periodontics/statistics & numerical data , Pressure , Reproducibility of Results
14.
J Accid Emerg Med ; 16(6): 428-30, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10572816

ABSTRACT

OBJECTIVES: To compare the clinical course and complications of snake bite in children and adults. METHODS: A retrospective review of 66 patients (28 children and 38 adults) admitted after snake bites for management at the Prince Abdullah Hospital in Bisha, in the south western part of Saudi Arabia, during the period May 1992 to May 1995. RESULTS: No significant difference was found in time of bite, site of bite, and sex preference between adults and children. Local complications, such as tissue necrosis, were commoner in children (14%) than in adults (5%). Systemic manifestations were also more commonly seen in children than in adults; this is possibly due to a higher ratio of injected venom to body mass in children. Leukocytosis was seen in 54% of children (adults 13%), a low haemoglobin concentration in 14% of children (adults 11%), prolonged prothrombin and partial thromboplastin times in 41% of children (adults 16%), while a high creatine phosphokinase was seen in 31% of children compared with 17% of adults. CONCLUSIONS: Children seem to have more serious local and systemic complications than adults and this may indicate the need to use a higher dose of antivenom than that being used at present.


Subject(s)
Snake Bites/epidemiology , Snake Bites/physiopathology , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Child , Child, Preschool , Emergency Service, Hospital/statistics & numerical data , Female , Humans , Infant , Leukocytosis/epidemiology , Male , Middle Aged , Retrospective Studies , Saudi Arabia/epidemiology , Severity of Illness Index , Sex Distribution , Snake Bites/classification , Snake Bites/complications
15.
Am J Nephrol ; 19(5): 552-4, 1999.
Article in English | MEDLINE | ID: mdl-10575182

ABSTRACT

It has previously been reported that in adult patients with sickle-cell anemia the serum phosphate value and the maximum tubular reabsorption of phosphate per liter of glomerular filtrate (TmP/GFR) were significantly higher than in normal controls. This does not appear to have been studied in children with sickle cell anemia (young sicklers) and this prompted us to assess renal phosphate reabsorption in this group of patients. We looked at serum phosphate level and calculated renal phosphate reabsorption (TP/GFR) in children taking random urine and blood samples at the same time and using the formula TP/GFR = Sp - Up x SCr: UCr, in 30 young sicklers all of whom had normal renal function (mean age 7.3 years) and 40 normal matching controls (mean age 6.5 years). The mean serum phosphate value in young sicklers was significantly lower than in controls (4.3 against 5.3 mg/dl) while the mean value of TP/GFR was 4.09 +/- 0.74 mg/dl in young sicklers compared to 4.65 +/- 0.75 mg/dl in the control group (p = 0.0026). Therefore, the TP/GFR in young sicklers was also significantly lower (p = 0.0026) than in the control group. This may be explained by the high serum level of parathyroid hormone reported previously in patients with sickle cell anemia which is expected to lower phosphate reabsorption (TmP/GFR and TP/GFR are identical in children). The lower serum phosphate value and TP/GFR in younger sicklers seems to be in contrast with the relatively high serum phosphate value and TP/GFR previously reported in adults with sickle cell anemia.


Subject(s)
Anemia, Sickle Cell/metabolism , Kidney Tubules/metabolism , Phosphates/metabolism , Absorption , Biomarkers/blood , Biomarkers/urine , Child , Child, Preschool , Creatinine/blood , Creatinine/urine , Female , Glomerular Filtration Rate , Humans , Male
16.
Saudi J Kidney Dis Transpl ; 8(3): 294-7, 1997.
Article in English | MEDLINE | ID: mdl-18417809

ABSTRACT

Sixty two children aged 12 years or below, with chronic renal failure (CRF) were admitted to Asir Central Hospital, Saudi Arabia, in the period from June 1990 to June 1995. Of them, 39 (63%) were in CRF while 23 (37%) were in end-stage renal failure (ESRF) at the time of presentation giving a mean annual incidence for CRF of 15.6 and for ESRF of 9.2 per million children. The male to female ratio was 1.8:1. The mean age of the children was 5.5 years (age range 20 days to 12 years). Urinary system anomalies (including urinary tract anomalies) were the leading cause of CRF (64.5%) followed by gloraerulopathies (17.7%). In those who presented before the age of six years, SO.9% had CRF caused by urinary system anomalies (including inherited kidney anomalies such as polycystic disease) while such anomalies accounted for only 30% of CRF in children older than six years. Glomerulopathies were the leading cause (45%) of CRF in this latter group. We conclude that our mean annual incidence of CRF and ESRF is high and urinary system anomalies constitute the commonest cause among children in our region. Early diagnosis should therefore be encouraged to ensure early treatment of these anomalies, thus decreasing the incidence of CRF.

17.
Ann Pharmacother ; 31(4): 432-4, 1997 Apr.
Article in English | MEDLINE | ID: mdl-9101004

ABSTRACT

OBJECTIVE: To report a case of hypocalcemia and hypomagnesemia after ibuprofen overdose. CASE SUMMARY: A 21-month-old boy developed acute renal failure with severe metabolic acidosis after ingestion of ibuprofen 8 g. The infant developed tonic-clonic seizures 46 hours after ingestion, with significant hypocalcemia and hypomagnesemia that required electrolyte replacement to control the seizures. DISCUSSION: To our knowledge this is the first case report of hypocalcemia, hypomagnesemia, and seizures in a patient after ibuprofen overdose. The mechanism is unclear, the situation was probably aggravated by the use of sodium polystyrene sulfonate and furosemide. CONCLUSIONS: In patients with ibuprofen overdose, serum calcium and magnesium concentrations should be evaluated since seizures may be associated with a deficiency of these cations. The management of these patients should include calcium and/or magnesium supplementation when required and furosemide should be avoided.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/poisoning , Hypocalcemia/chemically induced , Ibuprofen/poisoning , Magnesium/blood , Acidosis/chemically induced , Acidosis/complications , Drug Overdose , Humans , Hypocalcemia/complications , Infant , Male , Renal Insufficiency/chemically induced , Renal Insufficiency/complications , Seizures/chemically induced , Seizures/complications
18.
Ann Trop Paediatr ; 17(1): 101-3, 1997 Mar.
Article in English | MEDLINE | ID: mdl-9176586

ABSTRACT

An infant who had Turner syndrome with left renal agenesis and right hydronephrosis due to functional ureteropelvic junction obstruction is reported. The importance of routine imaging for early identification of potentially serious renal anomalies in patients being evaluated for short stature and possible Turner syndrome is emphasized.


Subject(s)
Kidney/abnormalities , Turner Syndrome/complications , Ureteral Obstruction/congenital , Female , Humans , Hydronephrosis/etiology , Infant , Ureteral Obstruction/complications
19.
Am J Nephrol ; 17(1): 68-71, 1997.
Article in English | MEDLINE | ID: mdl-9057956

ABSTRACT

In 48 children (aged 3-19 years; 33 males and 15 females), who underwent renal transplantation, the glomerular filtration rates (GFR) estimated from creatinine clearance involving urine collection over 4 h in the hospital under direct supervision and creatinine clearance predicted from plasma creatinine concentrations and height (formula) were compared with the GFR estimated by 99mTc-diethylenediamine penta-acetate (99mTc-DTPA) clearance. There was a good correlation between the three methods (r = 0.8). Measured and formula creatinine clearances overestimated the GFR as determined by 99mTc-DTPA by an average of 19.7 +/- (SD) 21.2 and 21.9 +/- 22.9 ml/min/1.73 m2, respectively. So they should be used with caution to estimate the true GFR. In trying to assess the influence of ciclosporin on creatinine secretion by renal tubules, we compared creatinine clearance in two groups of patients with similar GFR as measured by 99mTc-DTPA, and there was no significant difference in the mean values (p < 0.54) among patients on ciclosporin and azathioprine and on azathioprine alone. It seems, therefore, that ciclosporin did not cause an increased tubular secretion of creatinine leading to an overestimation of the GFR.


Subject(s)
Glomerular Filtration Rate , Kidney Transplantation/physiology , Azathioprine/therapeutic use , Child , Creatinine/metabolism , Cyclosporine/therapeutic use , Female , Humans , Immunosuppressive Agents/therapeutic use , Kidney Function Tests/methods , Male , Radioisotope Renography , Technetium Tc 99m Pentetate
20.
East Afr Med J ; 73(3): 191-3, 1996 Mar.
Article in English | MEDLINE | ID: mdl-8698020

ABSTRACT

This is a retrospective study of 55 children with Henoch-Schoenlein syndrome (HSS) admitted to Asir Central Hospital in the southern part of Saudi Arabia from September 1988 to September 1994. Of the 55 children studied, 29 were girls and 26 were boys with the ratio of 1.1:1. The ages ranged from eight months to 18 years with a mean of 8.6 +/- 5 years. Seventy three percent of our patients were older than five years at initial presentation. Most of the cases occurred between July and January. Hundred percent had the typical rash, 78% had abdominal pain on presentation with significant gastrointestine bleed in 11%. Seventy six percent had joint pain or discomfort. Twenty percent had renal involvement on initial presentation. Recurrence of HSS occurred in 13%. Our study does not show any major regional differences, except the fact that our patients seems to be older at time of presentation.


Subject(s)
IgA Vasculitis , Adolescent , Age Distribution , Child , Child, Preschool , Diagnosis, Differential , Female , Humans , IgA Vasculitis/complications , IgA Vasculitis/diagnosis , IgA Vasculitis/epidemiology , IgA Vasculitis/etiology , Infant , Male , Population Surveillance , Residence Characteristics , Retrospective Studies , Saudi Arabia/epidemiology , Seasons , Sex Distribution
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