Heterologous Two-Dose Vaccination with Simian Adenovirus and Poxvirus Vectors Elicits Long-Lasting Cellular Immunity to Influenza Virus A in Healthy Adults.

BACKGROUND: T-cell responses against highly conserved influenza antigens have been previously associated with protection. However, these immune responses are poorly maintained following recovery from influenza infection and are not boosted by inactivated influenza vaccines. We have previously demonstrated the safety and immunogenicity of two viral vectored vaccines, modified vaccinia virus Ankara (MVA) and the chimpanzee adenovirus ChAdOx1 expressing conserved influenza virus antigens, nucleoprotein (NP) and matrix protein-1 (M1). We now report on the safety and long-term immunogenicity of multiple combination regimes of these vaccines in young and older adults. METHODS: We conducted a Phase I open-label, randomized, multi-center study in 49 subjects aged 18-46years and 24 subjects aged 50years or over. Following vaccination, adverse events were recorded and the kinetics of the T cell response determined at multiple time points for up to 18months. FINDINGS: Both vaccines were well tolerated. A two dose heterologous vaccination regimen significantly increased the magnitude of pre-existing T-cell responses to NP and M1 after both doses in young and older adults. The fold-increase and peak immune responses after a single MVA-NP+M1 vaccination was significantly higher compared to ChAdOx1 NP+M1. In a mixed regression model, T-cell responses over 18months were significantly higher following the two dose vaccination regimen of MVA/ChAdOx1 NP+M1. INTERPRETATION: A two dose heterologous vaccination regimen of MVA/ChAdOx1 NP+M1 was safe and immunogenic in young and older adults, offering a promising vaccination strategy for inducing long-term broadly cross-reactive protection against influenza A. FUNDING SOURCE: Medical Research Council UK, NIHR BMRC Oxford.

Passive sexual transmission of human immunodeficiency virus type 1 variants and adaptation in new hosts.

Human immunodeficiency virus type 1 (HIV-1) genetic diversity is a major obstacle for the design of a successful vaccine. Certain viral polymorphisms encode human leukocyte antigen (HLA)-associated immune escape, potentially overcoming limited vaccine protection. Although transmission of immune escape variants has been reported, the overall extent to which this phenomenon occurs in populations and the degree to which it contributes to HIV-1 viral evolution are unknown. Selection on the HIV-1 env gene at transmission favors neutralization-sensitive variants, but it is not known to what degree selection acts on the internal HIV-1 proteins to restrict or enhance the transmission of immune escape variants. Studies have suggested that HLA class I may determine susceptibility to HIV-1 infection, but a definitive role for HLA at transmission remains unproven. Comparing populations of acute seroconverters and chronically infected patients, we found no evidence of selection acting to restrict transmission of HIV-1 variants. We found that statistical associations previously reported in chronic infection between viral polymorphisms and HLA class I alleles are not present in acute infection, suggesting that the majority of viral polymorphisms in these patients are the result of transmission rather than de novo adaptation. Using four episodes of HIV-1 transmission in which the donors and recipients were both sampled very close to the time of infection we found that, despite a transmission bottleneck, genetic variants of HIV-1 infection are transmitted in a frequency-dependent manner. As HIV-1 infections are seeded by unique donor-adapted viral variants, each episode is a highly individual antigenic challenge. Host-specific, idiosyncratic HIV-1 antigenic diversity will seriously tax the efficacy of immunization based on consensus sequences.

[Comparison of clinical results of anterior cruciate ligament reconstruction using two different procedures].

During the last two decades the "golden standard" in reconstruction of anterior cruciate ligament knee was the middle third of patellar tendon, but now are more used hamstrings tendon autograft. The aim of this work was to compare our results of the artroscopic reconstruction ACL (anterior cruciate ligament) of the knee using two different technics. We were controling 60 patients within the period of two years after operation. Group A was composed of 39 patients which had reconstructed ACL done with bone-patella tendon- bone autografts, in the group B were 21 patients and at them as autographts have been used hamstring tendon. Difference between healthe and the ill knee by the Lachman's test after operation, in the group A was 2,4 mm, but in the group B was 2,2mm (p> 0,05 ). Postoperative middle value of the Lysholm and Gillquist score in the group A was 97,74, in the group B it was 96,67 (p>0,05). IKDC score results are following: Group A- mark A 32 patients (84,6%); mark B 5 (12,8%); mark C 1 (2,6%) and in the group B: mark A 17 patients (81%); mark B 3 (14,28%): mark C 1 (4,72%) (p> 0,05). Postoperative value for the Tegner and Lyscholm score activity in the A group was 8,23, in B group it was 8,81. The reconstruction of ACL with bone- patella tendon-bone grafts gave better results then the reconstruction with the hamstring tendon only according to Tegner score values. In other parameters between those two groups there was no statisticaly significant difference.

[Dimensions of deciduous and permanent incisors in cases with Class II division 1 and 2 malocclusions]. / Dimenzije mlijecnih i trajnih sjekutica u ispitanika s anomalijom Klase II/1 i Klase II/2.

The analysis of mesiodistal dimensions of the upper and lower incisors (in total and separately) has been carried out in order to investigate the interdependence of sizes of the teeth with defined malocclusions. The investigation included 180 cases of both sexes, out of which 90 had deciduous dentition and other 90 examinees had permanent dentition. There were 120 examinees with Class II malocclusion (60 with Class II/1, and 60 with Class II/2), whereas the rest of 60 examinees with normal occlusion were used as the control group. Gnathometric measurements were made on the plaster casts with calipher precision of 0.1 mm and were double checked. Computer analysis of the results obtained emphasized the following: the heterogeneity of findings in the deciduous dentition does not allow hypothesis of a connection between sizes of the deciduous incisors and defined malocclusions; in the permanent dentition the examinees with Class II division 1 malocclusion have significantly the largest incisors, and the smallest the examinees with class II division 2 malocclusion; the greatest difference in the size between the deciduous and permanent incisors was found in the examinees with Class II division 1 malocclusion and the smallest difference was found in the examinees with normal occlusion.

[The changes of the occlusal relationship from deciduous to the permanent dentition in the longitudinal sample]. / Promjene okluzijskih odnosa na prijelazu mlijecne u trajnu denticiju kod longitudinalno pracenog uzorka.

The examination of the dynamics of the changes in sagittal, vertical and transversal occlusal relationship has been carried out on the sample of the 66 examinees of the both sexes. The children were examined for the first time at the age of 3.7 years, the again three times repeatedly (within a year) during the first period of the change of teeth. The occlusal changes were registered on the plaster models using the regular standard equipment. The results of the examination of the 4 gnathometric variables (class, overjet, overbite and the transversal occlusal relationship) have demonstrated the following: in 50% examinees the class remained unchanged; the total number of the examinees with class II as well as with uneven occlusal relationship, in the right and left quadrant have increased visibly; the early findings of class II have demonstrated very high stability; the inclination toward the increase of the overjet has been higher in the relation to the reduction; somewhat greater number has been recorded in the group on the overjet above 3 mm; overbite in the major part of the examinees has become deeper; the change from the open, tete a tete, minimal bite to the normal and deep bite has been recorded; the transversal occlusal relationship have remained unchanged in 60% of the cases; the frequency of the new transversal disarrangement in the mixed dentition has been three times higher in the relation to the earlier findings; also the cases of the spontaneous correction of the transversal disarrangement in the deciduous dentition have been recorded.

[Dynamics of the growth of craniofacial structures-a longitudinal study]. / Dinamika rasta kraniofacijalnih struktura-longitudinalna studija.

The frequency of basal cranial and facial forms, and of craniofacial indices, was analyzed to obtain some additional information on the craniofacial growth during a dynamic interval of the conversion of primary into mixed dentition. A sample of 72 children aged 3.5-5.5 years, free of any symptoms of orthodontic anomalies, were re-evaluated at the age of 6.5-8.5 years. The children were divided into groups according to anomalies possibly present on the second examination. Analysis of the subject distribution into cranial and facial forms revealed slight alterations during the period of observation. Therefore, analysis of the magnitude and frequency of index alterations was also included in the study. These analyses led to a conclusion that changes in the craniofacial form were quite frequently present but their intensity was too low for a subject to be allocated to the other basal group. A relationship between the craniofacial form alteration and maxillary morphology specific for particular anomaly could also be discerned. Thus, alterations in each individual dimension included in the indices, occurring during the mentioned interval, should be analyzed to shed more light upon the problem.

[Gnathometric changes in examinees with and without early findings of crowding--a longitudinal study]. / Gantometrijske promjene u ispitanika sa i bez ranog nalaza kompresije--longitudinalna studija.

The longitudinal sample of children of both sexes (31 without crowding and 39 with crowding) has been investigated to examine the influence of clinically estimated findings in the deciduous dentition in the volume of jaw growth as well as in the occurrence of some malocclusions in the mixed dentition. The children were examined for the first time at the age of 4.5 and again 3 years later. The results have pointed out the following: there was no essential difference in the volume of transversal and sagittal jaw growth in reference to early findings; in both groups the significant enlargement of transversal and sagittal dimensions was recorded; mean of the width of the upper dental arch are significantly higher in the group without crowding in primary dentition; mean of the length of the upper dental arch are somewhat higher in the examinees with early findings of crowding at the first examination, namely in the examinees without early finding of crowding at the second examination; mean of the overjet are somewhat higher in the group with early finding of crowding; distribution of the examinees in the mixed dentition according the orthodontic diagnosis does not show essential differences in regard to early finding; the largest number of the examinees in the mixed dentition shows the symptoms of the primary crowding regardless of the earlier findings; only 29.1% examinees without early finding of crowding, maintain the same characteristic in the mixed dentition; in the 26.4% examinees with early finding of crowding, there comes to the spontaneous loss of the primary symptoms during the change of teeth namely to the transfer to the group with no crowding.

[Growth dynamics of the four main craniofacial dimensions in relation to orthodontic finding--a longitudinal study]. / Dinamika rasta cetiri osnovne kraniofacijalne dimenzije s obzirom na ortodontski nalaz--longitudinalna studija.

Analysis of growth dynamics of the four main craniofacial dimensions at the transition point from primary into mixed dentition was performed in order to better determine the effect of individual orthodontic anomalies starting to manifest at that time, on the direction and extent of the alterations observed. A sample consisting of 73 children aged 3.5-5.5 years, free of any overt symptoms of orthodontic anomalies, were re-examined at the age of 6.5-8.5 years and divided into groups according to orthodontic findings then obtained. Mean values (and their differences) of the defined parameters obtained on the first and second measurement were analyzed, both for the sample in total and separately, according to the orthodontic findings in mixed dentition. Based on this data, specific relationships between alterations in each craniofacial dimension and maxillary morphology, specific for particular anomaly, were determined. In the group free of growth dynamics anomalies, both facial and both cranial parameters were almost identical. More or less expressed alterations of a single facial or cranial parameter in dysgnathic subjects may have been related to oral symptoms of the respective anomaly. At the same time, results obtained in the study suggested the size of the four main craniofacial dimensions to differ as early as in primary dentition, and become grouped, depending on the development of future orthodontic anomaly.

[Fracture of a transfixed intramedullary nail in a patient with pseudoarthrosis of the femoral diaphysis]. / Prelom transfiksiranog intramedularnog klina u bolesnika s pseudoartrozom dijafize femura.

This is a case report on a patient with a multiple femur's fracture where a transfixed intramedullar nailing of Grosse-Kempf type has been done. "The nail dynamization" was not carried out before the beginning of vertical loading. Seven months after the full vertical loading had begun, at a sudden torsian movement of the extremity, the nail had broken. Analyzing the cause of the fixative material fracture, a conclusion has been made that, apart from the presence of adequate trauma, the nail fracture happened also due to the development of pseudoarthrosis of femur and the unfulfilled "nail dynamization".

[Operative versus conservative treatment of the fractures or dislocations of the thorocolumbar spine associated with neurological deficiency]. / Operaciono i konzervativno lecenje fraktura ili dislokacija torakolumbalnog dela kicme udruzenih s neuroloskim ostecenjem.

The results of treatment of injuries of the thoracic and lumbar spine with neurological involvement, have been rewieved in a retrospective study of 42 patients, of whom 14 received conservative and 28 surgical treatment. Operations were reserved for patients with grossly unstable fracture, fracture-dislocations and pure dislocations. Open reduction and short internal fixation with Roy-Camille plates, were the operative procedures of choice. After the period of "bed rest" conservative treatment 71% of the patients showed clinical instability and 64% constant spinal pain. Only one (3%) operated patient had redeplacement and kyphotic angulation of the injured thoracolumbar spine. Of the patients treated conservatively 56% showed recuperation of the incomplete neurological lesions, as compared as to 53% of those treated surgically. Cases with complete neurological involvement showed some, but statistically significant, improvement only in the operated group of patients. It is concluded that surgical approach had obvious advantages about degree of the complete lesions neural recovery, final stability of the vertebral column and local pain symptoms.

[An analysis of craniofacial changes from deciduous to the first stage of mixed dentition]. / Analiza kraniofacijalnih promjena od mlijecne, do prve etape mjesovite denticije.

Analysis has been done, with intention to observe dynamic of craniofacial changes, from deciduous to the end of the first phase of the mixed dentition. In the longitudinal sample, consisted of 67 children both sexes, observed from 3.5 to 8.5 year of age, the determined measurements of craniofacial variables, and indexes of the skull and face, were examined. The figures were elaborated statistically. Results show the slow reduction of the brachiocephals, while the frequency of mesiocephalics increases, especially at girls, what measurement of indexes confirm. From the deciduous period to the beginning of the mixed dentition, slow growth of the number of euriprosops and reduction of mesioprosops was found, while during the deciduous dentition the situation was opposite. Analysis of each craniofacial dimension shows that the length and the width of cranium are reduced until the beginning of the mixed dentition and increased after that. The other variables show continued increase of dimensions, especially at last period. Correlations are significant and very significant, between the width of the skull and the upper width of the face (and less significant at lower width of the face, which is in a high degree correlated with the height, than between the length of cranium and the height of the face. It is confirmed by factor analysis. At the multivariate analysis, two or three varimax factors can be isolated, dependent on phases: factor of wideness, factor of length height, and factor of age.

[Craniometric and gnathometric characteristics of anomalies Angle Class II in deciduous dentition]. / Kraniometrijske i gnatometrijske osobitosti anomalija Klase II. u mlijecnoj denticiji.

The study was performed in 30 subjects with class II/1 and 30 subjects with class II/2 anomalies. The aim of the study was to assess the extent to which class II anomalies influenced individual craniometric and gnathometric dimensions as well as to determine whether there were any significant differences between the two subgroups. Craniometric dimensions were measured in each subject by means of standard measuring devices, while gnathometric analysis was carried out on plaster casts of their dental arches. Statistical processing was performed on an IBM PC-AT computer, with a SPSS/PC program support. The study results indicated the maxillomandibular and craniofacial growth to follow a specific pattern as early as in the deciduous dentition in subjects with class II anomalies. Differences between class II subgroups manifested in the range of the following parameters: all transversal craniometric dimensions were greater in class II/2, which was statistically significant in case of Eu-Eu dimension; height of the maxillary part of the face was significantly greater in class II/2; horizontal incisal step was significantly greater in class II/1; although all transversal dimensions of dental arches were considerably greater in class II/2, the differences were not statistically significant; the upper and lower dental arches were longer in class II/1 and II/2, respectively.

Polymorphism in codon 17 of the CTLA-4 gene (+49 A/G) is not associated with susceptibility to rheumatoid arthritis in British Caucasians.

The role of the CTLA-4 antigen in the development of autoimmune diseases is well documented, with several autoimmune disorders showing association or linkage with the CTLA-4 locus. Its role in the aetiology of rheumatoid arthritis (RA) however, remains unclear, as the functional studies of the B7-CTLA-4 pathway in mouse models of RA and genetic studies in humans have given contrasting results. We have studied the single nucleotide polymorphism at position +49 (A/G) of the CTLA-4 gene, in a cohort of 421 RA cases and 452 healthy controls from the UK. Despite the high statistical power to detect even a weak susceptibility effect, no significant association was found. We also analysed the distribution of the allele and genotype frequencies with respect to the presence of the shared epitope (a known RA susceptibility factor) and found no statistically significant differences. We conclude that, although the importance of the B7-CTLA-4 interaction in the development of RA can not be excluded, the CTLA-4 gene is unlikely to be a predisposing factor to this disease.

[Therapy of infected pseudarthroses of the lower leg]. / Lecenje inficiranih pseudoartroza potkolenice.

The retrospective study comprised 23 patients with infected pseudoarthrosis after osteosynthesis of of the lower log fracture treated at the Clinic of Orthopedic Surgery and Traumatology in Novi Sad. Staphylococcus aureus has been the most common causative agent of infection. In all patients debridment of infection foci was performed and reosteosynthesis with the external fixator and in 10 patients spongioplasty was performed in addition. At the control examination good results were achieved in 4, satisfying in 3 and poor in 16 patients. Amputation was performed in 5 patients.

[The value of local administration of antibiotics in treatment of bone infections]. / Vrednost lokalne primene antibiotika u lecenju infekcije kosti.

An open, controlled, randomized clinical investigation was carried out in 33 patients suffering from osteomyelitis. In the first group, 17 patients, a through drainage with sterile physiologic solution was applied, while in the second group, 16 patients, antibiotic was added to the sterile physiologic solution. In all patients values of C reactive protein (CRP) in the blood were examined, and later on every third day after the operation. A significant difference of average values of CRP between the 3rd and 21st day in both groups of patients was established, as well as the similarity in average values of CRP, which points to the fact that the mechanical effect of through drainage is dominant, speaking about rinsing focus of infection and eliminating necrotic tissues and small sequesters.

[Evaluation of long-term prognosis in patients with whiplash syndrome]. / Mogucnosti procene udaljene prognoze bolesnika s "whiplash" sindromom.

We reviewed 50 patients who sustained whiplash injuries of the neck. The mean time of the follow-up was 3 years. Only 16% of observed cases recovered completely. Residual symptoms were severe in 38%. Pain in the neck, headache and paraesthesia were the commonest complaints. Older patients and patients with significantly restricted movements of the neck, sharp local kyphotic deformity, chronic instability and neurologic involvement had a worse prognosis.

[Osteomyelitis after malleolar fractures]. / Osteomijelitis posle preloma maleolusa.

Over a ten-year period, 485 patients suffering from malleous fracture were operated at the Department for Orthopaedic Surgery and Traumatology in Novi Sad. Postoperative infection appeared in ten cases (2.06%). Eight of these patients primarily had open fractures, and two of them had closed ones. Osteosynthesis of the lateral malleous had most frequently been treated by the use of panel and screws. Staphylococcus aureus was isolated as symptom of the infection in eight cases. In treatment of malleous osteomyelitis, the debridement of focus of infection together with fixation material extraction was the most frequently performed operative method. During a two-year period no exacerbation, seven patients was observed while at control examination three patients had secretion from fistula. Mobility of ankle joint was limited in most cases, while walking imposed no pain.

[Comparative radiographic analysis of surgical and conservative treatment of unstable injuries of the thoracic and lumbar spine]. / Uporedna radiografska analiza operativnog i konzervativnog tretmana nestabilnih povreda torakalne i lumbalne kicme.

INTRODUCTION: Treatment of fractures and dislocations of the thoracolumbar spine is aimed at achieving a stable and painless spine. Concerning mode of treatment therapists are divided into two groups--those for conservative approach and those who advocate operative stabilization of spinal column. The objective of this paper was to compare radiological findings of both modes of treatment on the basis of our clinical material. MATERIALS AND METHODS: The examination included radiographs of 96 patients with radiolographic signs of unstable spine, treated at Clinic of Orthopaedic Surgery and Traumatology of the Institute of Surgery of the Clinical Center in Novi Sad from 1984 to 1998. Among 48 operated patients (average age of 40.7), there were more females--25, and among nonoperated, there were more males--33. The average age of conservatively treated patients was 52. Dynamic radiographs evaluated the angle of local kyphosis on the spot of injury (Cobb's angle), reduction of dimensions of the body of injured vertebra and sagittal movement of the body on affected level. Measured values were corrected by values of sagittal index. RESULTS: Initially the average angle of local kyphosis among operated was 26.9, among conservatively treated it was 19.7. Control values for operated were 14.7 and for conservatively treated 25.6. Initially, a wedge-shaped deformity larger than half of the front part of the injured vertebra body had 42 nonoperated and 32 operated patients. Initially, the average sagittal movement of the injured vertebra body among operated patients was 6.97 mm, and at control 1.34 mm. Among nonoperated, the average movement of the body was 1.71 mm initially and 3.23 mm at control. DISCUSSION: Similar results of angular deformity were found by other examiners. Their results are also in favor of operative treatment of unstable injuries of Th-L spine. The number of those proclaiming good results of conservative treatment of injures of thoracolumbar spine in patients with initially high values of angular deformity is much less. Willen, Mumford, Andreycik and others using wedge-shaped deformity and sagittal movement of the body as parameters in their studies had similar results as those in this study, and they conclude that the stability of segment is much higher among operated patients and that operative treatment finally ends in better radiological results. CONCLUSION: Radiological results of operative treatment of unstable injuries of thoracolumbar and lumbar spine are better than those of conservative treatment. In order to obtain a stable spine, which is the aim of treatment of unstable spine injuries, operative stabilization is necessary.