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1.
Hepatology ; 61(1): 88-97, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24797101

RESUMEN

UNLABELLED: High rates of sexually transmitted infection and reinfection with hepatitis C virus (HCV) have recently been reported in human immunodeficiency virus (HIV)-infected men who have sex with men and reinfection has also been described in monoinfected injecting drug users. The diagnosis of reinfection has traditionally been based on direct Sanger sequencing of samples pre- and posttreatment, but not on more sensitive deep sequencing techniques. We studied viral quasispecies dynamics in patients who failed standard of care therapy in a high-risk HIV-infected cohort of patients with early HCV infection to determine whether treatment failure was associated with reinfection or recrudescence of preexisting infection. Paired sequences (pre- and posttreatment) were analyzed. The HCV E2 hypervariable region-1 was amplified using nested reverse-transcription polymerase chain reaction (RT-PCR) with indexed genotype-specific primers and the same products were sequenced using both Sanger and 454 pyrosequencing approaches. Of 99 HIV-infected patients with acute HCV treated with 24-48 weeks of pegylated interferon alpha and ribavirin, 15 failed to achieve a sustained virological response (six relapsed, six had a null response, and three had a partial response). Using direct sequencing, 10/15 patients (66%) had evidence of a previously undetected strain posttreatment; in many studies, this is interpreted as reinfection. However, pyrosequencing revealed that 15/15 (100%) of patients had evidence of persisting infection; 6/15 (40%) patients had evidence of a previously undetected variant present in the posttreatment sample in addition to a variant that was detected at baseline. This could represent superinfection or a limitation of the sensitivity of pyrosequencing. CONCLUSION: In this high-risk group, the emergence of new viral strains following treatment failure is most commonly associated with emerging dominance of preexisting minority variants rather than reinfection. Superinfection may occur in this cohort but reinfection is overestimated by Sanger sequencing.


Asunto(s)
Antivirales/uso terapéutico , Infecciones por VIH/complicaciones , Hepacivirus/genética , Hepatitis C/virología , Proteínas Virales/genética , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Humanos , Interferón-alfa/uso terapéutico , Masculino , Recurrencia , Ribavirina/uso terapéutico , Análisis de Secuencia de ARN , Insuficiencia del Tratamiento
2.
Am J Clin Oncol ; 47(3): 99-104, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-37981697

RESUMEN

OBJECTIVES: Stereotactic Body Radiotherapy (SBRT) and Yttrium-90 (Y90) are among the ablative therapies used as treatment options for localized hepatocellular carcinoma (HCC). To date, direct comparisons of the 2 modalities' outcomes and costs are lacking. This study aimed to analyze demographic, treatment, and cost information for patients with HCC treated with SBRT and Y90. METHODS: Patients with HCC treated with SBRT or Y90 radioembolization between January 2018 and January 2020 at one institution were retrospectively reviewed. Demographic and treatment data were compared utilizing χ 2 tests. Kaplan-Meier curves and log-rank tests were applied to compare overall survival and progression-free survival in different treatment groups. Cox proportional hazard models were applied to analyze the unadjusted and adjusted survival differences. Ten SBRT and 10 Y90 patients were randomly selected for Medicare cost analysis. RESULTS: Sixty-three patients received Y90, and 21 received SBRT. On univariable and multivariable analysis, there was no significant difference in overall survival or progression-free survival between the Y90 and SBRT cohorts. SBRT patients had higher American Joint Committee on Cancer staging ( P =0.039), greater tumor size (4.07 vs. 2.96 cm, P =0.013), and greater rates of prior liver-directed therapy (71.4% SBRT vs. 12.7% Y90, P <0.001). The average cost for SBRT was $15,148, and Y90 was $41,360. CONCLUSIONS: SBRT and Y90 are effective therapies in the treatment of HCC, specifically having similar overall survival and progression-free survival. Y90 was found to have a significantly higher cost than SBRT. This study demonstrates the need for prospective studies to assess these modalities in treating HCC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Radiocirugia , Radioisótopos de Itrio , Humanos , Anciano , Estados Unidos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Estudios Retrospectivos , Estudios Prospectivos , Medicare , Resultado del Tratamiento
3.
Malar J ; 12: 279, 2013 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-23927596

RESUMEN

BACKGROUND: Malaria is a leading cause of mortality in southern Benin. The main causative agent, Plasmodium falciparum, poses a threat on critical transfusions in pregnant women and children. This study's objective was to compare the performance of different malaria screening methods in blood donors in southern Benin, a malaria-endemic country. METHODS: Blood from 2,515 voluntary blood donors in Benin was collected over a period of 10 months in ethylenediaminetetraacetic acid (EDTA) tubes, which were then classified according to extraction time: long rainy season, short dry season, short rainy season, and long dry season. Microscopic examination was used to count parasites. Parasite density (PD) was expressed as the number of parasites per µL of blood. Pan Plasmodium pLDH detection was assessed by an ELISA-malaria antigen test. Using crude soluble P. falciparum antigens, an ELISA-malaria antibody test detected anti-Plasmodium antibodies. RESULTS: Among the 2,515 blood donors (2,025 males and 488 females) screened, the rate of asymptomatic Plasmodium carriage was 295/2,515 (11.72%, 95% CI: 10.5-13.1%). Males had a higher infection rate (12.4%) than did females (8.8%). Parasite density was very low: between seven and100 parasites per µL of blood was reported in 80% of donors with parasitaemia. Three Plasmodium species were diagnosed: P. falciparum in 280/295 patients (95.0%), Plasmodium malariae in 14/295 (5.0%), and Plasmodium ovale in 1/295 (0.34%). Malaria prevalence in donors was higher during the rainy seasons (13.7%) compared with the dry seasons (9.9%). The use of a highly sensitive assay enabled pan Plasmodium pLDH detection in 966/2,515 (38.4%, 95% CI: 36.5%-40.3%). Malaria antibody prevalence was 1,859/2,515 (73.9%, 95% CI: 72.16-75.6%). Donors' antigenaemia and antibody levels varied significantly (P <0.05) over the course of the four seasons. The highest antigenaemia rate 323/630 (51.3%), was observed during the short rainy season, while the highest antibody prevalence, 751/886 (84.7%), was recorded during the long dry season. CONCLUSION: Blood donations infected with Plasmodium can transmit malaria to donation recipients. Malaria diagnostic methods are currently available, but the feasibility criteria for mass screening in endemic areas become preponderant. Detection of the pLDH antigen seems to be an adequate screening tool in endemic areas, for this antigen indicates parasite presence. Routine screening of all donated blood would prevent infected blood donations and reduce P. falciparum transmission in critical patients, such as children and pregnant women. This tool would also decrease medical prophylaxis in donation recipients and contribute to lower Plasmodium resistance.


Asunto(s)
Antígenos de Protozoos/sangre , Donantes de Sangre , Sangre/parasitología , Técnicas de Laboratorio Clínico/métodos , L-Lactato Deshidrogenasa/sangre , Tamizaje Masivo/métodos , Plasmodium/enzimología , Adolescente , Adulto , Anciano , Anticuerpos Antiprotozoarios/sangre , Antígenos de Protozoos/inmunología , Benin , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Humanos , L-Lactato Deshidrogenasa/inmunología , Malaria/diagnóstico , Masculino , Microscopía/métodos , Persona de Mediana Edad , Plasmodium/aislamiento & purificación , Adulto Joven
4.
J Saudi Heart Assoc ; 35(4): 279-289, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38116404

RESUMEN

Introductions: The awareness of brain death and heart donation (HD) among the Saudi population remains limited, coupled with negative attitudes toward heart donation, resulting in a significant gap between the demand for donor hearts and the available supply. This study aimed to comprehensively understand the current perceptions, attitudes, and practices of the Saudi population regarding HD, as well as identify the obstacles. The ultimate goal was to strengthen the local donor pool. Methods: A cross-sectional study was conducted from March to May 2023, employing a self-administered internet survey. The survey collected demographic information, assessed awareness, attitudes, and practices related to HD, and was completed by 1820 participants from various regions in Saudi Arabia. Data was analyzed using SPSS version 25 (SPSS Inc., Chicago, Illinois, USA). Chi-square test, Independent-samples t-test, one way analysis of variance test (ANOVA) and Spearman correlation coefficient was performed with the significance level set at p < 0.05. Results: A significant portion of the population (out of 1820 participants) lacked organ donation cards and were uncertain about the registration process. Participants displayed a moderate level of knowledge about HD, with roughly half holding unfavorable attitudes toward HD. A considerable percentage of participants 62.0% were unwilling to register as heart donors, but a majority (79.9%) were willing to contribute by disseminating information about HD. The study identified significant associations between knowledge scores and several factors, including age (p = 0.002), career (p = 0.000), possession of an organ donation card (p = 0.000), and a history of transplantation or organ donation among relatives (p = 0.000). A significant relationship was observed between attitude scores and several factors, including career (p = 0.001), Saudi region (p = 0.025), possession of an organ donation card (p = 0.000), and a history of transplantation or organ donation among relatives (p = 0.000). Conclusion: The study highlights the urgent need for increased awareness to bolster the number of local heart donors. The involvement of healthcare professionals and social campaigns is essential to enhance public knowledge and potentially boost the willingness of individuals to become donors.

5.
J Infect Dis ; 203(1): 18-24, 2011 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-21148492

RESUMEN

We describe the first confirmed person-to-person transmission of oseltamivir-resistant pandemic influenza A(H1N1) 2009 virus that occurred in a hematology unit in the United Kingdom. Eleven cases of (H1N1) 2009 virus infection were identified, of which, ten were related as shown by sequence analysis of the hemagglutinin and neuraminidase genes. H275Y analysis demonstrated that 8 of 10 case patients had oseltamivir-resistant virus, with 4 of 8 case patients infected by direct transmission of resistant virus. Zanamivir should be considered as first-line therapy for influenza in patients with lymphopenic hematological conditions and uptake of influenza vaccination encouraged to further reduce the number of susceptible individuals.


Asunto(s)
Antivirales/farmacología , Farmacorresistencia Viral , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Gripe Humana/transmisión , Gripe Humana/virología , Oseltamivir/farmacología , Adulto , Anciano , Sustitución de Aminoácidos/genética , Infección Hospitalaria/transmisión , Infección Hospitalaria/virología , Hemaglutininas Virales/genética , Hospitales , Humanos , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Linfopenia/complicaciones , Persona de Mediana Edad , Mutación Missense , Neuraminidasa/genética , ARN Viral/genética , Análisis de Secuencia de ADN , Reino Unido , Proteínas Virales/genética
6.
Cureus ; 14(12): e32124, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36601220

RESUMEN

BACKGROUND: Nowadays patients are encouraged to partake in healthcare decision making and patient preferences are given increasing weight. Patient's choice is important to reduce waiting time and to encourage competition between providers, as most patients look for high-quality care while minimizing costs, according to different studies this may not be as simple as the attributes and factors that patients value when selecting a hospital or surgeon. Overall, Saudi Arabia has minimal research on how patients select surgeons or surgical facilities. Therefore, the goal of the current study was to evaluate the criteria Saudi population patients used to select their surgeons. OBJECTIVE: The objective is to determine the relative importance of the following aspects that patients may consider when selecting a surgeon: (a) physician-related considerations; (b) elements relating to healthcare service and access; (c) the perspectives of patients on various factors. METHODS: This observational cross-sectional study attempts to investigate the criteria that people in Saudi Arabia considered most important while selecting their surgeons. This study was conducted between August and November 2022. The questionnaire is also given in English along with Arabic. RESULTS: Six hundred nine completed the survey with a response rate of 91.6%. Concerning physician-related factors considered when choosing a surgeon attitudes of the physician were the factor most significantly contributed to physician selection rather than reputation or professional experience and physician social media: (84.7%) mentioned that paying attention to patient's needs and opinions is important; sparing enough time for patients is important as reported by 83.9% of the participants; Personal care and hygiene is important for 83.4% of the participants; Communication skills were considered to be important as stated by 82.6% of the participants. Regarding healthcare services/access-related factors considered by patients in physician selection; it was found that patients considered hospital hygiene-cleanliness (91.3 %) as the most significant healthcare service/access-related factor in physician selection and then it comes Ease of obtaining an appointment (89.7%), reasonable scheduling and wait for time (87.7%) and cost of surgery (82.1%). Physician selection was deemed crucial to the success of the therapy by 87.7% of patients, while 88.3% of patients thought it was crucial to research the doctor before contacting her or him for the current admission. CONCLUSION: Patients consider a wide range of variables when selecting their surgeons and the location of their procedure. Depending on sociodemographic, cultural, and other aspects, the conditions surrounding patients' decisions may vary. Overall, the selection of a surgeon by surgery patients appears to be more influenced by the doctor's attitudes than by his or her reputation, professional experience, or social media presence. In order to elicit preferences across a wider range of surgical subspecialties and patient demographics, more study is necessary.

7.
Cureus ; 14(8): e28017, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36120246

RESUMEN

Introduction One contributing factor that has led to a reduction in the number of females entering the profession of surgery is discrimination against female surgeons. Little is known about the practices, attitudes, and perceptions of the Saudi population toward gender discrimination in the field of surgery. The aim of this study was to assess the practices, attitudes, and perceptions of the Taif population in choosing a surgeon based on their gender. Materials and methods An online pretested questionnaire was randomly sent to the participants living in Taif city. Collected data were subjected to scrutiny to check participants' study inclusion criteria. All the data were subjected to statistical analysis by an independent biostatistician. Pearson's chi-square test was used to search for a statistically significant association between categorical variables. Results About 49.5% of the participants preferred a surgeon of the same gender when consulting for a non-emergency visit to a surgery clinic, whereas females significantly preferred a female surgeon (p < 0.001). The most common reason to choose surgeons of the same gender was comfort, followed by ease of talking. About 71.8% of the participants preferred female surgeons for ''sensitive'' surgical cases such as genital, obstetric, or sexual disorders, whereas 12.1% preferred male surgeons. Conclusion Females have shown progress in the field of surgery, but there is still much to be done to convert the surgical workplace to be more supportive of women so that they contribute their best effort.

9.
Cureus ; 13(5): e15318, 2021 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-34221767

RESUMEN

BACKGROUND: Epidemiological data regarding the causes, patterns, severity, and outcomes of traumatic brain injury (TBI) are essential to plan for preventive strategies addressing this public health epidemic. The main aim of this study is to explore the patterns and causes of traumatic brain injury at two trauma centers. METHODS: A retrospective cohort study was conducted using a pre-tested validated data collection sheet. Data were collected from the medical records and electronic database of patients who presented to the emergency department with head trauma. Variables including the mechanisms, patterns of the injury, accompanying injuries, level of consciousness, and hospitalization duration were investigated for any possible association. RESULTS: A total of 269 patients (78% males, 22% females) who satisfied our study criteria were included in the final analysis. Motor vehicle collisions were the most common reason for traumatic brain injury (57.6%) followed by falls (28.3%). There was a statistically significant association observed between type of hemorrhage and Glasgow coma scale at initial presentation (P < 0.05).  Conclusion: The most common cause of traumatic brain injury is motor vehicle collisions, followed by falls. The public should be made aware of the importance of using safety and precautionary measures to minimize the impact of traumatic brain injuries. Educational programs for neurotrauma prevention can be developed and utilized as a blueprint for local hospitals and officials in the country.

10.
Exp Parasitol ; 124(2): 190-6, 2010 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19755119

RESUMEN

Congenital infection is one of the most serious settings of infection with the apicomplexan parasite Toxoplasma gondii. Ocular diseases, such as retinochoroiditis, are the most common sequels of such infection in utero. However, while numerous studies have investigated the physiopathology of acquired toxoplasmosis, congenital infection has been largely neglected so far. Here, we establish a mouse model of congenital ocular toxoplasmosis. Parasite load and ocular pathology have been followed for the first 4 weeks of life. Ocular infection developed slowly compared to cerebral infection. Even after 4 weeks, not all eyes were infected and ocular parasite load was low. Therefore, we evaluated a scheme of neonatal infection to overcome problems associated with congenital infection. Development of infection and physiopathology was similar, but at a higher, more reliable rate. In summary, we have established a valuable model of neonatal ocular toxoplasmosis, which facilitates the research of the underlying physiopathological mechanisms and new diagnostic approaches of this pathology.


Asunto(s)
Modelos Animales de Enfermedad , Toxoplasmosis Ocular/congénito , Animales , Animales Recién Nacidos , Encéfalo/parasitología , ADN Protozoario/análisis , Ojo/parasitología , Ojo/patología , Femenino , Masculino , Ratones , Parasitemia/parasitología , Reacción en Cadena de la Polimerasa , Embarazo , Complicaciones Parasitarias del Embarazo/parasitología , Organismos Libres de Patógenos Específicos , Toxoplasma/genética , Toxoplasma/aislamiento & purificación , Toxoplasmosis Animal/congénito , Toxoplasmosis Animal/parasitología , Toxoplasmosis Cerebral/parasitología , Toxoplasmosis Ocular/parasitología
11.
Br J Radiol ; 93(1115): 20200257, 2020 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-32706980

RESUMEN

OBJECTIVE: To evaluate the multiparametric MRI in predicting chemotherapy response in pathologically proven cases of osteosarcoma and Ewing's sarcoma. Correlation between the tumor size changes and internal breakdown using RECIST 1.1, modified RECIST, quantitative apparent diffusion coefficient (ADC) and tumor volume as well as dynamic contrast-enhanced MRI (DCE-MRI). METHODS: The study included 104 patients pathologically proved osteosarcoma (53) and Ewing`s sarcoma (51) underwent MRI examinations; before and after chemotherapy. All patients were assessed using the RECIST 1.1 criteria, m-RECIST, quantitative ADC, and tumor volume evaluation. 21 patients underwent DCE-MRI curve type with quantitative parameters. Correlation between the different evaluations was carried out. Results were correlated with the post-operative pathology in 42 patients who underwent surgery and for statistical evaluation, Those patients were classified into responders (≥90% necrosis) and non-responders (<90% necrosis). RESULTS: The initial mean ADC of 104 patients of osteosarcoma and Ewing's sarcoma (0.90 ± 0.29) and (0.71 ± 0.16) respectively, differed significantly from that after treatment (1.62 ± 0.46) and (1.6 ± 0.39) respectively with (p<0.001).ADC variations (ADC%) in the non-progressive group were higher than those of the progressive group (128.3 ± 63.49 vs 36.34 ± 78.7) % with (p<0.001).ADC values and ADC variations were inversely correlated with morphologic changes, regardless of the effectiveness of chemotherapy expressed as changes in tumor size based on (RECIST 1.1, RECIST, and 3D volume). Linear regression analysis revealed a Pearson correlation coefficient of r=-0.427, -0.498 and -0.408, respectively with (p<0.001).An increase in the ADC value was not always associated with a reduction in tumor volume. The disease control rate (defined as the percentage of CR+PR+SD patients) was 89.4% and 93.9% according to RECIST 1.1 and m-RECIST respectively.42 out of the 104 patients had postsurgical histological evaluation as regards the chemotherapeutic response divided into two groups. ADC values showed a statistically significant difference between Group A and Group B being more evident with minimum ADC% (p<0.001). CONCLUSION: Quantitative diffusion-weighted imaging with ADC mapping and ADC % after chemotherapy allows a detailed analysis of the treatment response in osteosarcoma and Ewing's sarcoma. The therapeutic response can be underestimated using RECIST 1.1, so the modified RECIST should be also considered. ADVANCES IN KNOWLEDGE: Quantitative ADC especially ADC% provided an accurate non-invasive tool in the assessment of post-therapeutic cases of osteosarcoma and Ewing's sarcoma.


Asunto(s)
Neoplasias Óseas/tratamiento farmacológico , Imagen de Difusión por Resonancia Magnética , Imágenes de Resonancia Magnética Multiparamétrica , Osteosarcoma/tratamiento farmacológico , Sarcoma de Ewing/tratamiento farmacológico , Adolescente , Adulto , Área Bajo la Curva , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/patología , Neoplasias Óseas/cirugía , Niño , Preescolar , Medios de Contraste , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteosarcoma/diagnóstico por imagen , Osteosarcoma/patología , Osteosarcoma/cirugía , Estudios Prospectivos , Curva ROC , Criterios de Evaluación de Respuesta en Tumores Sólidos , Sarcoma de Ewing/diagnóstico por imagen , Sarcoma de Ewing/patología , Sarcoma de Ewing/cirugía , Resultado del Tratamiento , Carga Tumoral/efectos de los fármacos , Adulto Joven
12.
J Clin Virol ; 119: 60-67, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31431408

RESUMEN

BACKGROUND: Globally, hepatitis E virus (HEV) is a major cause of acute viral hepatitis. Epidemiology and clinical presentation of hepatitis E vary greatly by location and are affected by the HEV genotype. Nucleic acid amplification technique (NAT)-based assays are important for the detection of acute HEV infection as well for monitoring chronic cases of hepatitis E. OBJECTIVES: The aim of the study was to evaluate a panel of samples containing different genotypes of HEV for use in nucleic NAT-based assays. STUDY DESIGN: The panel of samples comprises eleven different members including HEV genotype 1a (2 strains), 1e, 2a, 3b, 3c, 3e, 3f, 4c, 4g as well as a human isolate related to rabbit HEV. Each laboratory assayed the panel members directly against the 1st World Health Organization (WHO) International Standard (IS) for HEV RNA (6329/10) which is based upon a genotype 3 a strain. RESULTS: The samples for evaluation were distributed to 24 laboratories from 14 different countries and assayed on three separate days. Of these, 23 participating laboratories returned a total of 32 sets of data; 17 from quantitative assays and 15 from qualitative assays. The assays used consisted of a mixture of in-house developed and commercially available assays. The results showed that all samples were detected consistently by the majority of participants, although in some cases, some samples were detected less efficiently. CONCLUSIONS: Based on the results of the collaborative study the panel (code number 8578/13) was established as the "1st International Reference Panel (IRP) for all HEV genotypes for NAT-based assays" by the WHO Expert Committee on Biological Standardization. This IRP will be important for assay validation and ensuring adequate detection of different genotypes and clinically important sub-genotypes of HEV.


Asunto(s)
Técnicas de Laboratorio Clínico/normas , Virus de la Hepatitis E/genética , Virus de la Hepatitis E/aislamiento & purificación , Hepatitis E/diagnóstico , Técnicas de Amplificación de Ácido Nucleico/normas , Genotipo , Hepatitis E/virología , Virus de la Hepatitis E/clasificación , Humanos , Cooperación Internacional , Filogenia , ARN Viral/genética , Estándares de Referencia , Reproducibilidad de los Resultados , Organización Mundial de la Salud
13.
Malar J ; 6: 19, 2007 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-17313669

RESUMEN

BACKGROUND: The methods most commonly used to measure malarial antibody titres are the Indirect Fluorescence Antibody Test (IFAT), regarded as the gold standard, and the Enzyme-Linked ImmunoSorbent Assay (ELISA). The objective here was to assess the diagnostic performance, i.e. the sensitivity and specificity, of a new malaria antibody ELISA kit in comparison to IFAT. This new ELISA kit, the ELISA malaria antibody test (DiaMed), uses a combination of crude soluble Plasmodium falciparum extract and recombinant Plasmodium vivax antigens. METHODS: Two groups were used: 95 samples from malaria patients to assess the clinical sensitivity and 2,152 samples from blood donors, who had not been exposed to malaria, to assess the clinical specificity. RESULTS: The DiaMed ELISA test kit had a clinical sensitivity of 84.2% and a clinical specificity of 99.6% as compared with 70.5% and 99.6% respectively, using the IFAT method. The ELISA method was more sensitive than the IFAT method for P. vivax infections (75% vs. 25%). However, in 923 malaria risk donors the analytical sensitivity of the ELISA test was 40% and its specificity 98.3%, performances impaired by large numbers of equivocal results non-concordant between ELISA and IFAT. When the overall analytical performances of ELISA was compared to IFAT, the ELISA efficiency J index was 0.84 versus 0.71 for IFAT. Overall analytical sensitivity was 93.1% and the analytical specificity 96.7%. Overall agreement between the two methods reached 0.97 with a reliability k index of 0.64. CONCLUSION: The DiaMed ELISA test kit shows a good correlation with IFAT for analytical and clinical parameters. It may be an interesting method to replace the IFAT especially in blood banks, but further extensive investigations are needed to examine the analytical performance of the assay, especially in a blood bank setting.


Asunto(s)
Anticuerpos Antiprotozoarios/sangre , Ensayo de Inmunoadsorción Enzimática/métodos , Malaria/diagnóstico , Plasmodium/inmunología , Animales , Antígenos de Protozoos/aislamiento & purificación , Donantes de Sangre , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Malaria Vivax/diagnóstico , Plasmodium falciparum/inmunología , Plasmodium vivax/genética , Plasmodium vivax/inmunología , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/aislamiento & purificación , Sensibilidad y Especificidad , Estadística como Asunto
14.
J Clin Virol ; 65: 50-3, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25766988

RESUMEN

BACKGROUND: Protease inhibitors (PI) including boceprevir, telaprevir and simeprevir have revolutionised HCV genotype 1 treatment since their introduction. A number of pre-treatment resistance associated amino acid variants (RAVs) and polymorphisms have been associated with reduced response to treatment. OBJECTIVES: We measured the prevalence of RAVs/polymorphisms in a PI treatment-naïve HCV genotype 1 Scottish cohort using Sanger sequencing. STUDY DESIGN: Chronically infected, treatment-naïve, HCV genotype 1 patients (n = 146) attending NHS Greater Glasgow and Clyde clinics were investigated for RAVs/polymorphisms to the PIs boceprevir, telaprevir and simeprevir. The NS3/4A region was amplified by nested polymerase chain reaction. The 1.4 kb amplified product was sequenced using an ABI 3710XL DNA sequencer. Sequence analysis was performed using web-based ReCall (beta 2.10). Amino acid positions 36, 41, 43, 54, 55, 80, 109, 122, 155, 156, 168 and 170 were analysed for RAVs/polymorphisms. RESULTS: Overall, 23.29% (34/146) of patients had an RAV or polymorphism detected. Overall, 13.69% (20/146) of patients had HCV virus that contained the Q8 K polymorphism. Other RAVs detected were: V36 M 0.70% (1/146), V36L 0.70% (1/146), T54S 6.85% (10/146), V55A 3.42% (5/146) and V/I170A 0.68% (1/146). Four patients had dual combinations of mutations (T54S+V36L; T54S+V55A and 2 patients with T54S+Q80K). CONCLUSIONS: Q80K was the most prevalent baseline polymorphism detected in the Scottish cohort. Simeprevir treatment is not recommended in patients infected with the Q80K genotype 1a variant. This highlights the need for baseline sequencing prior to administration of this drug in this population.


Asunto(s)
Sustitución de Aminoácidos , Hepatitis C Crónica/virología , Mutación/efectos de los fármacos , Polimorfismo Genético , Proteínas no Estructurales Virales/genética , Antivirales/farmacología , Farmacorresistencia Viral , Femenino , Genotipo , Hepacivirus/genética , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Masculino , Oligopéptidos/farmacología , Reacción en Cadena de la Polimerasa , Prevalencia , Prolina/análogos & derivados , Prolina/farmacología , Escocia , Análisis de Secuencia de ADN , Simeprevir/farmacología , Proteínas no Estructurales Virales/química
15.
AIDS ; 27(15): 2485-8, 2013 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-23770494

RESUMEN

NS3 protease inhibitors are set to improve sustained virological response rates in HIV-positive patients with hepatitis C. We measured the prevalence of natural resistance polymorphisms in 38 acutely infected treatment-naive patients using direct and deep sequencing. Twenty six percent of patients (10/38) had a majority variant resistance mutation (in order of frequency; Q80K - 16%, V36M - 5%, T54S - 3%, V55A - 3%, and D168A - 3%). Low-frequency mutations were detected in all samples. Further studies are required to determine threshold levels associated with treatment failure.


Asunto(s)
Hepacivirus/genética , Hepatitis C/genética , Polimorfismo Genético/genética , ARN Viral/genética , Enfermedad Aguda , Infecciones por VIH/complicaciones , Hepatitis C/complicaciones , Humanos
16.
J Biol Chem ; 284(1): 119-133, 2009 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-18984589

RESUMEN

Designed histidine-rich amphipathic cationic peptides, such as LAH4, have enhanced membrane disruption and antibiotic properties when the peptide adopts an alignment parallel to the membrane surface. Although this was previously achieved by lowering the pH, here we have designed a new generation of histidine-rich peptides that adopt a surface alignment at neutral pH. In vitro, this new generation of peptides are powerful antibiotics in terms of the concentrations required for antibiotic activity; the spectrum of target bacteria, fungi, and parasites; and the speed with which they kill. Further modifications to the peptides, including the addition of more hydrophobic residues at the N terminus, the inclusion of a helix-breaking proline residue or using D-amino acids as building blocks, modulated the biophysical properties of the peptides and led to substantial changes in toxicity to human and parasite cells but had only a minimal effect on the antibacterial and antifungal activity. Using a range of biophysical methods, in particular solid-state NMR, we show that the peptides are highly efficient at disrupting the anionic lipid component of model membranes. However, we also show that effective pore formation in such model membranes may be related to, but is not essential for, high antimicrobial activity by cationic amphipathic helical peptides. The information in this study comprises a new layer of detail in the understanding of the action of cationic helical antimicrobial peptides and shows that rational design is capable of producing potentially therapeutic membrane active peptides with properties tailored to their function.


Asunto(s)
Antiinfecciosos/química , Antimaláricos/química , Péptidos Catiónicos Antimicrobianos/química , Péptidos/química , Membrana Celular/química , Histidina/química , Concentración de Iones de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Estructura Secundaria de Proteína , Relación Estructura-Actividad
17.
J Infect Dis ; 199(8): 1239-49, 2009 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-19302012

RESUMEN

BACKGROUND: Uveitis is a major cause of visual impairment throughout the world. Analysis of cytokine profiles in aqueous humor specimens may provide insight into the physiopathological processes that underly retinal damage in this context. METHODS: Using a multiplex assay, we determined the concentrations of 17 cytokines and chemokines in aqueous humor specimens obtained from patients with ocular toxoplasmosis or viral uveitis and compared these concentrations with those in specimens obtained from patients with noninfectious intermediate uveitis or cataract. RESULTS: Five mediators (interleukin [IL]-8, monocyte chemoattractant protein-1, tumor necrosis factor-alpha, IL-4, and IL-10) were detected in >50% of patients in all groups. In contrast, IL-5 and IL-12 were specific for ocular toxoplasmosis, and granulocyte monocyte colony-stimulating factor and IL-1 were specific for viral uveitis; these mediators could present specific markers for diagnostic purposes. Interferon-gamma, IL-6, and macrophage inflammatory protein-1beta were common markers of ocular toxoplasmosis and viral uveitis. IL-17 was a common marker of ocular toxoplasmosis and intermediate uveitis. CONCLUSIONS: We found specific cytokine profiles for each type of uveitis, with large interindividual variations and no etiological or clinical correlations. Ocular cytokine mapping contributes to a better understanding of the physiopathology of specific forms of uveitis and provides guidance for new targeted treatment.


Asunto(s)
Citocinas/metabolismo , Infecciones Virales del Ojo/inmunología , Toxoplasmosis Ocular/inmunología , Uveítis/parasitología , Uveítis/virología , Adolescente , Adulto , Anciano , Humor Acuoso/química , Citocinas/sangre , Citocinas/genética , Femenino , Perfilación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Análisis de Secuencia de Proteína , Uveítis/inmunología , Adulto Joven
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