Polimorfismos de los genes CCR5, IL-6, IFN-γ e IL-10 en pacientes cubanos con VIH/sida / Polymorphisms of CCR5, IL-6, IFN-γ and IL-10 genes in Cuban HIV/AIDS patients

Introducción Los estudios genéticos han demostrado asociaciones de varios polimorfismos de un solo nucleótido (SNP) con diferentes tasas de progresión y variación en la susceptibilidad a la infección por VIH. Este estudio tuvo como objetivo estimar la frecuencia de los polimorfismos ccr5Δ32, IL-6-174G/C, IFN-γ+874T/A e IL-10-1082A/G en pacientes cubanos infectados por VIH y un grupo de parejas serodiscordantes para evaluar su influencia sobre el riesgo y la progresión de la enfermedad. Métodos Se realizó un estudio transversal en 120 sujetos atendidos en el Instituto de Medicina Tropical «Pedro Kour» (IPK) y el Hospital Hermanos Ameijeiras entre junio de 2018 y diciembre de 2019. La amplificación de los fragmentos de los genes ccr5, IL-6, IFN-γ e IL-10 se realizó mediante reacción en cadena de la polimerasa seguida por el análisis del polimorfismo de fragmentos de restricción utilizando la enzima NlaIII para la IL-6. El sistema de mutación refractario a la amplificación por PCR se utilizó en el caso de los genes IFN-γ e IL-10. Resultados Las distribuciones alélicas y genotípicas de los genes ccr5, IL-6, IFN-γ e IL-10 no difirieron significativamente entre los dos grupos. Los recuentos celulares y los valores de carga viral en plasma no difirieron significativamente entre los genotipos de los genes ccr5, IL-6, IFN-γ e IL-10. Solo el genotipo IL-6 GC se asoció con valores más altos de carga viral. La combinación de alelos de los cuatro SNP considerados mostró un aumento muy significativo del riesgo de infección por VIH para uno de ellos, pero con una frecuencia muy baja (<1%). Conclusión Este estudio contribuye a evaluar la frecuencia de estos polimorfismos y su influencia en los biomarcadores de la progresión de la infección por VIH en la población cubana con infección por el VIH. (AU)

Introduction Genetic studies have shown associations of several single nucleotide polymorphisms (SNP) with different rates of progression and variation in susceptibility to HIV infection. This study aimed to estimate the frequency of ccr5Δ32, IL-6-174G/C, IFN-γ+874T/A and IL-10-1082A/G polymorphisms in Cuban HIV-infected patients and a group of sero-discordant couples to assess their influence on risk and disease progression. Methods A cross-sectional study was carried out on 120 subjects registered at the Institute of Tropical Medicine «Pedro Kour» (IPK) and the Ameijeiras Hospital from June 2018 until December 2019. The amplification of fragments of the ccr5, IL-6, IFN-γ and IL-10 genes was performed by polymerase chain reaction followed by identification of polymorphisms using the restriction fragment length polymorphism analysis for IL-6 with the restriction enzymes Nla III. Amplification refractory mutation system was used for IFN-γ and IL-10 genes. Results The allelic and genotypic distributions of the genes ccr5, IL-6, IFN-γ and IL-10 did not differ significantly between the two groups. Cell counts and plasma viral load values did not differ significantly between genotypes of the ccr5, IL-6, IFN-γ and IL-10 genes. Only the IL-6 GC genotype was associated with higher viral load values. The combination of alleles of the four considered SNPs showed a highly significant increase in the risk of HIV infection for one of them, but with a very low frequency (<1%). Conclusion This study contributes to evaluating the frequency of these polymorphisms and their influence on biomarkers of the progression of HIV infection in the Cuban HIV-population. (AU)

Polimorfismos de los genes CCR5, IL-6, IFN-γ e IL-10 en pacientes cubanos con VIH/sida / Polymorphisms of CCR5, IL-6, IFN-γ and IL-10 genes in Cuban HIV/AIDS patients

Introducción Los estudios genéticos han demostrado asociaciones de varios polimorfismos de un solo nucleótido (SNP) con diferentes tasas de progresión y variación en la susceptibilidad a la infección por VIH. Este estudio tuvo como objetivo estimar la frecuencia de los polimorfismos ccr5Δ32, IL-6-174G/C, IFN-γ+874T/A e IL-10-1082A/G en pacientes cubanos infectados por VIH y un grupo de parejas serodiscordantes para evaluar su influencia sobre el riesgo y la progresión de la enfermedad. Métodos Se realizó un estudio transversal en 120 sujetos atendidos en el Instituto de Medicina Tropical «Pedro Kour» (IPK) y el Hospital Hermanos Ameijeiras entre junio de 2018 y diciembre de 2019. La amplificación de los fragmentos de los genes ccr5, IL-6, IFN-γ e IL-10 se realizó mediante reacción en cadena de la polimerasa seguida por el análisis del polimorfismo de fragmentos de restricción utilizando la enzima NlaIII para la IL-6. El sistema de mutación refractario a la amplificación por PCR se utilizó en el caso de los genes IFN-γ e IL-10. Resultados Las distribuciones alélicas y genotípicas de los genes ccr5, IL-6, IFN-γ e IL-10 no difirieron significativamente entre los dos grupos. Los recuentos celulares y los valores de carga viral en plasma no difirieron significativamente entre los genotipos de los genes ccr5, IL-6, IFN-γ e IL-10. Solo el genotipo IL-6 GC se asoció con valores más altos de carga viral. La combinación de alelos de los cuatro SNP considerados mostró un aumento muy significativo del riesgo de infección por VIH para uno de ellos, pero con una frecuencia muy baja (<1%). Conclusión Este estudio contribuye a evaluar la frecuencia de estos polimorfismos y su influencia en los biomarcadores de la progresión de la infección por VIH en la población cubana con infección por el VIH. (AU)

Introduction Genetic studies have shown associations of several single nucleotide polymorphisms (SNP) with different rates of progression and variation in susceptibility to HIV infection. This study aimed to estimate the frequency of ccr5Δ32, IL-6-174G/C, IFN-γ+874T/A and IL-10-1082A/G polymorphisms in Cuban HIV-infected patients and a group of sero-discordant couples to assess their influence on risk and disease progression. Methods A cross-sectional study was carried out on 120 subjects registered at the Institute of Tropical Medicine «Pedro Kour» (IPK) and the Ameijeiras Hospital from June 2018 until December 2019. The amplification of fragments of the ccr5, IL-6, IFN-γ and IL-10 genes was performed by polymerase chain reaction followed by identification of polymorphisms using the restriction fragment length polymorphism analysis for IL-6 with the restriction enzymes Nla III. Amplification refractory mutation system was used for IFN-γ and IL-10 genes. Results The allelic and genotypic distributions of the genes ccr5, IL-6, IFN-γ and IL-10 did not differ significantly between the two groups. Cell counts and plasma viral load values did not differ significantly between genotypes of the ccr5, IL-6, IFN-γ and IL-10 genes. Only the IL-6 GC genotype was associated with higher viral load values. The combination of alleles of the four considered SNPs showed a highly significant increase in the risk of HIV infection for one of them, but with a very low frequency (<1%). Conclusion This study contributes to evaluating the frequency of these polymorphisms and their influence on biomarkers of the progression of HIV infection in the Cuban HIV-population. (AU)

Polymorphisms of CCR5, IL-6, IFN-γ and IL-10 genes in Cuban HIV/AIDS patients.

INTRODUCTION: Genetic studies have shown associations of several single nucleotide polymorphisms (SNP) with different rates of progression and variation in susceptibility to HIV infection. This study aimed to estimate the frequency of ccr5Δ32, IL-6-174G/C, IFN-γ+874T/A and IL-10-1082A/G polymorphisms in Cuban HIV-infected patients and a group of sero-discordant couples to assess their influence on risk and disease progression. METHODS: A cross-sectional study was carried out on 120 subjects registered at the Institute of Tropical Medicine «Pedro Kour¼ (IPK) and the Ameijeiras Hospital from June 2018 until December 2019. The amplification of fragments of the ccr5, IL-6, IFN-γ and IL-10 genes was performed by polymerase chain reaction followed by identification of polymorphisms using the restriction fragment length polymorphism analysis for IL-6 with the restriction enzymes Nla III. Amplification Refractory Mutation System was used for IFN-γ and IL-10 genes. RESULTS: The allelic and genotypic distributions of the genes ccr5, IL-6, IFN-γ and IL-10 did not differ significantly between the two groups. Cell counts and plasma viral load values did not differ significantly between genotypes of the ccr5, IL-6, IFN-γ and IL-10 genes. Only the IL-6 GC genotype was associated with higher viral load values. The combination of alleles of the four considered SNPs showed a highly significant increase in the risk of HIV infection for one of them, but with a very low frequency (<1%). CONCLUSION: This study contributes to evaluating the frequency of these polymorphisms and their influence on biomarkers of the progression of HIV infection in the Cuban HIV-population.

Total shoulder prosthesis with humeral resurfacing: Impact on lateral offset and short-term clinical consequences.

BACKGROUND: Reports of early glenoid wear after humeral resurfacing hemiarthroplasty have prompted the use, in combination with this procedure, of newly developed glenoid implants. This combination can increase global humeral offset. The objectives of this study were to assess changes in overall lateral offset and their potential short-term clinical consequences after combined humeral resurfacing and glenoid replacement. HYPOTHESIS: Combined humeral resurfacing and glenoid replacement induces a large increase in overall lateral offset, resulting in short-term clinical consequences. MATERIAL AND METHODS: A single-centre prospective study was started in November 2011. Consecutive patients scheduled for total shoulder arthroplasty with humeral resurfacing were included. The primary outcome measure was the change in lateral offset between radiographs obtained pre-operatively and 3 months post-operatively. The functional outcome assessed using the Constant score was compared between the groups with a lateral offset change <10mm vs. ≥10mm. RESULTS: From November 2011 to November 2014, 35 total shoulder arthroplasties with humeral resurfacing were performed in 32 patients with a mean age of 72.1 years (range, 55-86 years). Mean follow-up was 20±6 months (range, 12-31 months). Overall lateral offset was significantly greater post-operatively than pre-operatively (14±6mm vs. 5±7mm, p<0.0001), the mean difference being 8mm (range, 2-20mm). Post-operative range of motion was better in the group with an overall lateral offset ≥10mm (p=0.0016). DISCUSSION: Combined humeral resurfacing and glenoid replacement markedly increases overall lateral offset. This increase is not associated with adverse effects on short-term function and may improve post-operative motion range. However, greater lateral offset elevates the loads on the glenoid implant, which may increase the risk of glenoid implant loosening and rotator cuff tearing. Close radiological monitoring is therefore imperative. LEVEL OF EVIDENCE: IV, prospective cohort study.

Immune and protective abilities of ubiquitinated and non-ubiquitinated pseudorabies virus glycoproteins.

Plasmids encoding ubiquitinated (ubi-) or non-ubiquitinated (non-ubi-) glycoproteins of Pseudorabies virus (PRV) were used for vaccination of pigs. We found that the fusion of ubiquitin to viral glycoproteins increased their degradation in proteasomes in vitro, in which ubiquitin plays a key role. In the animals immunized with the plasmids encoding PRV ubi-glycoproteins and then challenged with PRV, we detected a slightly decreased cellular immune response on days 13 and 19 after immunization and a reduced nasal excretion of infectious virus on day 2 after the challenge. Afterwards, no effect of the ubiquitination of the glycoproteins on humoral or cellular immunity and on excretion of infectious virus was observed. Similarly, no effect of the ubiquitination on protective abilities of PRV glycoproteins was found.

[Trans-styloid and intrafocal pinning for extra-articular extension fractures of the distal radius: prospective randomized postoperative comparison with simple intra-focal pinning]. / Brochage mixte trans-styloïdien et intrafocal dans les fractures extra-articulaires en extension du radius distal: étude prospective randomisée de la stabilité postopératoire comparativement au brochage intra-focal simple.

PURPOSE OF THE STUDY: Intra-focal pinning as described by Kapandji in 1976 is generally standard treatment of fractures of the distal radius with posterior displacement. This technique, based on the bench effect of pinning on the posterior and radial cortexes has certain limitations in the event of major posterior comminution. In order to improve stability, other authors have proposed a modification of the Kapandji technique, replacing the lateral intra-focal pin with a direct trans-styloid pin. The purpose of this prospective radiographic study was to determine whether the modified Kapandji method improves the quality of postoperative reduction and provides a gain in stability. MATERIAL AND METHODS: This prospective radiographic study included 85 patients. The first group, composed of 41 patients, was treated with the standard intra-focal pinning using one or two dorsal pins and one lateral pin (group K). The second group of 44 patients was treated with one or two intra-focal pins and one lateral transfocal pin (group KM). The postoperative care was the same for the two groups. Clinical and radiographic assessment (lateral and AP views) was performed at day 21, at day 45 after removal of the pins, and at last follow-up. Two operators working independently from the surgeons measured the orientation of the radial surface on the lateral and AP views and the radioulnar variance at day 0, 21, 45 and last follow-up. RESULTS: Group K included 38 patients, mean age 57 years, and group KM 40 patients, mean age 53 years. Seven patients were lost to follow-up. The two groups were comparable regarding age, gender, type of lesion. The postoperative assessment showed radial inclination of 19.3 degrees on the AP view and 3 degrees on the lateral view with 6.6 degrees radiolulnar variance for the K group. The corresponding values were 22.2 degrees , 5.3 degrees and 12.2 degrees for the KM group. Postoperatively, there was a significant difference between the groups for radial glenoid on the AP view (p=0.004) and radiolulnar variance (p<0.0001) but there were no differences on the lateral view. At day 45 postop, mean values were 17.3 degrees AP and 1.1 degrees lateral for radial inclination and 2.2 degrees for radioulnar variance in the K group with 21 degrees , 4.7 degrees and 10 degrees in the KM group. There was a difference in group K for values measured on day 0 and day 45. There was no significant difference between the values on day 0 and day 45 for the KM group. DISCUSSION AND CONCLUSION: The purpose of this radiological assessment was to evaluate the efficacy of replacing the lateral intra-focal pin with a lateral transfocal pin in terms of primary stability of extra-articular fractures of the distal radius with posterior displacement. The results appear to show that this technique provides more sustained reduction during the first six weeks, particularly concerning radioulnar variance and radial glenoid inclination on the AP view, objectives needed for good clinical outcome. It also enables a notable improvement in postoperative stability while preserving the advantages of an easily reproducible minimally destructive percutaneous technique.

Risk assessment in new and conventional vaccines.

New technology, and in particular new molecular biology tools, have opened up access to new generations of vaccines or control tests. DNA vaccines are of particular interest since only the gene is injected and, as a consequence, specific risks are associated with this kind of vaccination. Some strategies are presented here to improve DNA vaccine efficacy, which can in some cases result in the reduction of the quantity of plasmid needed and therefore limits the risk. Specific tools to study the distribution of plasmids inside the body as well as tools to detect plasmid insertion inside the host genome have been developed. A final part of this paper will present briefly the new tools which have been or can be developed to detect contaminants in vaccines.

[Sympathectomy by phenol infiltration in the treatment of chronic obliterative arteriopathies of the lower limbs. Comparison between 60 statistical cases and 35 surgical sympathectomies (author's transl)]. / La sympathectomie au phénol dans le traitement des artériopathies chroniques oblitérantes des membres inférieurs. Comparaison d'une statistique de 60 cas avec 35 sympathectomies chirurgicales.

The authors compare the results obtained by the use of two different lumbar sympathectomy techniques in patients with chronic obliterative arterial disease of the lower limbs. Surgical resection was employed in 35 cases, and infiltration with phenol under radiological control in 60 cases. The proportion of successful results was about the same in both groups, best results being obtained in younger patients with less advanced disease. No mortality occurred in the group treated by phenol infiltration. Transient neuralgia was reported in some cases, but hospital stay was reduced by an average of 10 days, and many cases could be treated as out-patients. More than half of the patients did not require operation or amputation after phenol infiltration, which is, therefore, a very valuable associated therapeutic measure, especially in the elderly.