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.

Rheumatoid arthritis susceptibility and interleukin 10: a study of two ethnically diverse populations.

INTRODUCTION: IL-10 is an immunoregulatory cytokine which may modulate disease expression in rheumatoid arthritis (RA). The IL-10 gene is highly polymorphic with a number of single nucleotide polymorphisms in the promoter region and two microsatellite loci, IL10.R and IL10.G, 4 kb and 1.1 kb 5' of the transcription initiation site. It has been reported that allele 2 of the IL10.R microsatellite (IL10.R2) is associated with increased IL-10 secretion and IL10.R3 with reduced secretion. Subsequently, over-representation of IL10.R2 and under-representation of IL10.R3 in three independent RA groups has been reported. The aim of the current study is to determine whether there is an association between the IL10.R2 allele and RA in two ethnically distinct populations. METHODS: IL10.R genotypes were determined by semi-automated DNA sequencing technology in 186 UK Caucasians and 138 South Africans of Zulu or Sotho origin, fulfilling the 1987 American College of Rheumatology (ACR) criteria for RA. The Caucasian patients had relatively severe disease and comprised 75 patients with RA vasculitis, 22 with Felty's syndrome and 89 who had undergone a joint replacement (hip or knee) within 15 years of the onset of disease. Allele frequencies were compared with 296 Caucasians and/or 73 South Africans. RESULTS: The frequency of the IL10.R2 allele was significantly greater in the South Africans (RA and controls) than in the Caucasians (0.78 vs 0.66, P=1 x 10(-6)), while the frequency of IL10.R3 was less common (0.16 vs 0.3, P=1 x 10(-8)). No differences were observed in either IL10.R2 or IL10.R3 frequencies between patients and controls in either population. CONCLUSIONS: We were unable to confirm any association between IL10.R alleles and RA in this study. However, significant differences were demonstrated in the frequency of IL10.R2 and IL10.R3 between the two ethnic groups. The relatively high frequency of IL10.R2 in the South African population (0.78) would have reduced the power to detect an association with RA.

Non-inherited maternal HLA alleles are associated with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is strongly associated with a series of HLA-DRB1 alleles that encode a conserved sequence of amino acids ((70)Q/R K/R R A A(74)) in the DRbeta1 chain, known as the shared epitope (SE). However 30% of patients are negative for DRB1*04 and 15% are SE-negative. Exposure to these alleles as non-inherited maternal antigens (NIMA) might explain this discrepancy. We undertook a family study to investigate the role of NIMA in RA. METHODS: One hundred families, including the RA proband and both parents, were recruited. HLA-DRB1 genotyping was performed using an allele-specific polymerase chain reaction by standard methods. The frequencies of NIMA and non-inherited paternal antigens (NIPA) were compared using contingency tables and a two-tailed P test. We then reviewed four previously published studies of NIMA in RA and conducted an analysis of the combined data RESULTS: We identified 36 families in which the proband was DRB1*04-negative and 13 in which the proband lacked the SE. There was an excess of DRB1*04 and SE NIMA (P=0.05) compared with NIPA. Combined analysis with previous studies showed that 53/231 mothers (23%) versus 25/205 fathers (12%) had a non-inherited DRB1*04 (P=0.003) and 30/99 mothers versus 18/101 fathers had a non-inherited SE allele (P=0.03). CONCLUSION: A role for HLA NIMA in RA is suggested by these results.

The F158V polymorphism in FcgammaRIIIA shows disparate associations with rheumatoid arthritis in two genetically distinct populations.

OBJECTIVES: To investigate the association of the FcgammaRIIIA gene with rheumatoid arthritis (RA) in two genetically distinct groups: a white group from the United Kingdom and a northern Indian group. METHODS: The distributions of the two alleles of the FcgammaRIIIA F158V polymorphism were determined in 398 white patients from the United Kingdom and 63 Indian patients with RA and compared with those from 289 United Kingdom and 93 Indian healthy controls, respectively. RESULTS: Among the Indian patients, the frequency of the rare 158V allele and the proportion of 158VV homozygotes were reduced (relative risk (RR)=0.3, 95% confidence interval (95% CI) 0.1 to 1.1, p<0.06), reaching statistical significance for carrying the 158VV phenotype relative to 158FV or FF (RR=0.2, 95% CI 0.05-0.9, p<0.02). Conversely, no significant deviation in allelic frequencies was noted between the patients and controls from the United Kingdom. CONCLUSIONS: The 158VV phenotype showed a weak protective effect against developing RA in the Indian group. However, this sample was small (resulting in a low power for statistical analysis) and no independent confirmation was found in the larger white United Kingdom group. Thus the FcgammaRIIIA locus is unlikely to be of major importance in causing RA.

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.

Whole-genome screening in ankylosing spondylitis: evidence of non-MHC genetic-susceptibility loci.

Ankylosing spondylitis (AS) is a common inflammatory arthritis predominantly affecting the axial skeleton. Susceptibility to the disease is thought to be oligogenic. To identify the genes involved, we have performed a genomewide scan in 185 families containing 255 affected sibling pairs. Two-point and multipoint nonparametric linkage analysis was performed. Regions were identified showing "suggestive" or stronger linkage with the disease on chromosomes 1p, 2q, 6p, 9q, 10q, 16q, and 19q. The MHC locus was identified as encoding the greatest component of susceptibility, with an overall LOD score of 15.6. The strongest non-MHC linkage lies on chromosome 16q (overall LOD score 4.7). These results strongly support the presence of non-MHC genetic-susceptibility factors in AS and point to their likely locations.

[Soft tissue injuries of the neck]. / Povrede mekih tkiva vrata.

Thirty five patients were examined. All had soft tissue spinal cord injury and were not treated in a hospital. Complete diagnostic and therapeutical protocol was carried out only for 13 patients. The goal was to compare their initial condition with condition after the control examination after the therapy. Results showed that 8 patients (23%) suffered from pain in the neck, 25 (72%) had limited neck mobility, and 17 (49%) manifested neurological symptoms. Signs of osteochondrosis at isolated spinal levels and dyscoligamental instability were noted in one fifth of the observed patients. In 24 patients (69%) the condition was defined as "serious". Although soft tissue spinal cord injuries are considered as "light" injuries, they can cause serious consequences that reduce the quality of patient's life due to inadequate treatment. From that point of view, a serious approach to diagnosis and treatment is necessary.

[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.

[Arthroscopy of the knee--"surgery without complications"]. / Artroskopija kolena--"hirurgija bez komplikacija".

INTRODUCTION: Beside other advantages that arthroscopic surgery has, comparing to the open surgery, there is one more--the risk of complications is present but a very little. The aim of this work is to present complications that we have had and to point at possibilities how to prevent and treat them. MATERIAL, METHODS AND RESULTS: In the period from September 1990 to December 1998, 1071 arthroscopic surgeries were performed in our hospital. 817 patients (76%) were male and 254 (24%) female, average age 30.63 (12-69). Left knee was involved in 560, while the right in 511 cases. Among all arthroscopic interventions 463 (43.23%) were diagnosed when damages of LCA or cartilage were seen, and 608 (56.76%) were patients with therapeutic arthroscopic interventions. Among different arthroscopic interventions medial meniscectomy was performed in 417 (38.93%) patients, lateral in 124 (11.57%), removal of joint loose bodies in 39 (3.64%), reconstruction of LCA in 29 (2.70%), operation on patellar and condylar cartilage in 26 (2.42%) etc. There were 39 (3.64%) complications. 10 (25.64%) of them were intraoperative (breakage of arthroscopic instruments, loss of meniscal parts, extravasation of the fluid in extremity and 29 (74.35%) of them were postoperative (infection, synovial sinus, thrombophlebitis, haemarthrosis, synovial effusion, painful scar). 8 (1.72%) of those complications appeared after diagnostic arthroscopy and 31 (5.09%) after different therapeutic arthroscopic procedures. DISCUSSION: Advantages of arthroscopic surgery are exhibited in different ways (shortening hospital stay, lower cost of treatment, shortening the time necessary for complete recovery and return to everyday life and sport activities), while the risk of complications, although possible, is significantly diminished. Insufficient education, improvisation, rude manipulation, unprecise++ surgical approaches to the knee joint lead to aforementioned complications. Our results are discussed and compared to those found in the literature giving suggestions in the same time how to avoid and prevent them. CONCLUSION: Orthopedic surgeons who perform arthroscopic surgery must be well trained and familiar with the arthroscopic procedures and able to prevent and overcome possible complications. Continual education and training is necessary for arthroscopic surgeons in order to be able to follow innovations in surgical techniques and instrumentation.

Interethnic studies of TNF polymorphisms confirm the likely presence of a second MHC susceptibility locus in ankylosing spondylitis.

The objective of this study was to investigate TNF promoter region polymorphisms for association with susceptibility to ankylosing spondylitis (AS). The TNF -238 and -308 polymorphisms were genotyped in 306 English AS cases and 204 ethnically matched healthy B27-positive controls, and 96 southern German AS cases, 58 B27-positive and 251 B27-negative ethnically matched controls. Additionally, the TNF -376 polymorphism was genotyped in the southern German cases and controls. In the southern German AS patients a significant reduction in TNF -308.2 alleles was seen, compared with B27 positive controls (odds ratio 0.4, P = 0.03, 95% confidence interval 0.2-0.9), but no difference in allele frequencies was observed at TNF -238. Significant association between AS and both TNF -238 and TNF -308 was excluded in the English cases. These results confirm previous observations in the southern German population of association between TNF promoter region polymorphisms and AS, but the lack of association in the English population suggests that these polymorphisms themselves are unlikely to be directly involved. More likely, a second, non-HLA-B, MHC locus is involved in susceptibility to AS in these two populations.

[Evaluation of the usefulness of suction drainage in the treatment of nonspecific bone infections monitored with C-reactive protein]. / Procena uspesnosti protocne drenaze u lecenju nespecificne infekcije kosti pracenjem C-reaktivnog proteina.

INTRODUCTION: Irrigation suction drainage (ISD) is an additional method in treatment of infected bones. Two liters of saline solution daily with an antibiotic is usually recommended for ISD, although some authors suggest that more fluid should be used without antibiotics, stressing the importance of the mechanical effect. Although the method is nowadays accepted as a routine procedure, the reported results of ISD are based on treatment of a limited number of patients and the only criteria for assessment have been clinical and bacteriologic findings. The aim of this prospective study is to show the importance of the mechanical effect of an increased fluid run and the optimal time necessary for cleaning of the osteomyelitic cavity by follow-up the C-reactive protein (CRP) levels as an indicator of an acute inflammation of the affected bone. METHODS: The prospective study was an open, centralized and randomized clinical investigation including over 105 patients with bone infection treated in the period 1986-1996. Two parameters with possible influence on the CRP levels were determined during investigation: 1. patients were divided in three groups depending on the duration of the irrigation suction drainage (3-6 days, 7-10 days and over 10 days) and 2. quantity of the liquid used for the irrigation suction drainage (two groups: 2000 ml per day and 6000 ml per day). Groups were similar in regard to age, sex, bacteriologic agents, duration of infection, localization and previous operations. C-reactive protein (CRP) is a nonspecific, but extremely sensitive indicator of an acute inflammatory disease. The erythrocyte sedimentation rate is not always a reliable indicator of infection. CRP as a protein of an acute phase appears and disappears quickly. Decreased values are a sign of a healing process used in this study for the estimation of the efficacy of the ISD. The CRP level was controlled semiquantitatively before operation and every third day over three weeks. If the values were below 6 mg/l, the results were classified as negative. RESULTS: There were not significant statistical differences in different groups as far as a preoperative average CRP values were concerned neither in the quantity of employed liquid nor in the duration of the ISD and interaction between these two groups. It was the same on the third postoperative day. The differences appear in the significantly lower average values of the CRP in patients of the second group (6000 ml/day) where the ISD lasted for seven or more days. During further follow up, (6th to 21st day) one can observe a significant statistical difference in average CRP values between the first (2000 ml/day) and second group (6000 ml/day) but there is not difference when the duration and sort of employed liquid is concerned. There is not significant difference in average statistical values of the CRP in blood for interaction of fluid quantity and time of ISD as well. DISCUSSION: The main disadvantage in the function of ISD is nonuniform rinsing of the osteomyelitic cavity. Prolonged ISD has no influence on the clinical result as well as on the average values of the CRP. Starting from the third postoperative day results indicate that the quantity of employed liquid has an important influence on the average level of the CRP, while the duration of ISD is not important. Prolonged ISD can not compensate for an inappropriate surgical intervention because it is only an additional method in the treatment of an osteomyelitic process. CONCLUSION: By observing changes in CRP levels during treatment one can conclude that the efficacy of ISD is based mostly on mechanical rinsing and the removal of debris. This points to the importance of the quantity of fluid employed in irrigation suction drainage. Application of 6000 ml liquid per day without antibiotics during 5-7 days gives opportunity of better rinsing increasing the effect of ISD and reducing the incidence of complications.

[Arthroplasty in the treatment of congenital anomalies of the hip in adults]. / Artroplastika u lecenju kongenitalnih anomalija kuka u odraslih osoba.

At the Clinic for Orthopedic Surgery and Traumatology in Novi Sad, 79 adult patients with osteoarthritic hip dysplasia underwent total joint replacement surgery in the period 1984-1993. 45 patients were followed-up for an average time of 4.2 years. The results obtained have been evaluated following the criteria of Postel-Merle-d'Aubigne's hip rating system. After surgery 37 (82.2%) patients had minimal or no pain at all, while the hip flexion was over 75 degrees in 35 (75.5%) patients. 9% of patients could not walk longer than 20 minutes with a flexion under 50 degrees. Firm footfall and slight limp in exhaustion occurred in 35 (75.5%) patients, while 7 (15.5%) patients were extremely unstable and were able to get about on crutches. The gathered results confirm that total hip replacement in patients with osteoarthritic dysplastic hip improves stability and hip joint movement as well as pain reduction.

Craniofacial parameters during growth from the deciduous to permanent dentition--a longitudinal study.

Data on the dynamics of craniofacial growth, obtained by simple non-invasive measurements, are scarce in comparison with those collected by cephalometric methods. The aim of this study was to measure a number of craniofacial parameters, and to evaluate their changes during transition from the deciduous to the permanent dentition. A sample of 61 subjects (32 boys and 29 girls) were followed longitudinally by annual examination from an initial mean age of 4.7 years to a final mean age of 11.8 years. Conventional anthropometric instruments were employed to measure six craniofacial variables: G-Op, Eu-Eu, Zy-Zy, Go-Go, N-Gn and N-Pr. The data were analysed using basic summary statistics and a longitudinal regression model. A difference between males and females was found for all variables during the study period. During the transition from deciduous to mixed dentition (4.7-7.5 years), the cranial breadth and length (Eu-Eu and G-Op) decreased followed by an increase during the mixed dentition. All other parameters showed a continuous increase, which was highest for the variables defining facial height.

[Etiopathogenic, diagnostic and therapeutic aspects of stress fractures]. / Neki etiopatogenezni i dijagnosticko-terapijski aspekti stres fraktura.

Stress fractures occur with strenuous activity and represent a unique and relatively rare traumatic entity. Their diagnosis is difficult and therapy accompanied with specific problems. The purpose of the presented study is to explain basic characteristics of stress fractures and to approximate possibility of diagnosis and treatment better. Out of 26 fractures, 22 (84.62%) were nondisplaced and managed by bed rest, non-weight bearing or plaster of Paris immobilization for eight to ten weeks. On the other hand, four primarily displaced fractures (15.38%) were successfully treated with rigid internal fixation. Four conservatively managed patients (18.18%), two with fractures of the tibia and two with fractures of the femoral neck, attained a secondary angulation and pseudoarthrosis of the fracture site and, for these reasons, recorded injuries demanded a compensatory surgery management. It is suggested that in case of suspectability of stress fractures it is beneficial to use, parallel to native radiographic study, the bone scan imaging techniques which in the earlier phase of the disease establishes the diagnosis. Treatment of the stress fractures should be, as a rule, conservative. Moreover, "fatigue" fractures of the tibia and femoral neck ask for more continuous observations and a serious access. If non weightbearing regiment and immobilization do not decrease the difficulties; and fracture patterns progress, or if fracture becomes displaced because of delayed diagnosis, open reduction and rigid internal fixation should be done without delay.

[Fractures of the spine in patients with ankylosing spondylitis]. / Frakture kicme u bolesnika s ankiloznim spondilitisom.

Eight patients with spine fractures in chronic ankylosing spondylitis have been analyzed. The purpose of this article is to determine possibilities of spine injuries accompanied with this specific rheumatic disease and to show difficulties in diagnosis and problems in treatment. Ankylosing spondylitis affects spine in the way that it ossifficate ligaments, synovial joints and other soft tissue structures. Fractures that occur through these areas involve both bones and ligaments, producing an unstable condition, similar to a shearing type of classic spine injuries. The radiologic diagnosis of these injuries is difficult because the bone is frequently osteoporotic and displacement is of minor degree. In this study, 41.67% of the patients were not diagnosed initially and 16.67% were, for this reason, deteriorated neurologically. Therefore, patients known to have ankylosing spondylitis should be examined regarding the possibility of a fracture, and if pains persist after an injury, they should be thoroughly investigated radiologically to rule out a potentially serious problem. Reduction of the displacement and adequate stabilization, preferably by surgery, should be achieved whenever possible.

[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.

[Cytokines in bronchial asthma]. / Citokini u bronhijalnoj astmi.

Integracions among T cells, B cells and macrophages is central to the immune response. These cells produce a number of biologically active proteins, which form complex network of cell-to-cell interaction, and regulate proliferation and function of the immune systems. Cytokines act on variety of cells type in a non-antigen specific manner. Only helper cells receive antigen specific signal and convert them via lymphokines secretion into antigen-nonspecific mediators of immune response. The followings cytokines have been found in asthamic airways: IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, TNF-alfa, GM-CSH. CD+4 cells are major source of cytokines in astmatic airway. It has been identified that two subsets of helper cells (TH-1 and TH-2) exist, which secret different cytokines profils. Both produce IL-1, IL-3, GM-CSF and TNF-alfa. TH-1 produce IL-2, IFN-gamma and TNF-beta (LT). TH-2 cells produce IL-4, IL-5 and IL-10. IL-4 produced by activited TH-2 subset, mast cells, and basophils is enhanced in asthma and responsible for IgE synthesis and expresion of IgE Fc-R-II. TH-1 specific IFN-gamma inhibits IL-4 induced IgE synthesis whereas TH-2 specific IL-10 supresses IFN-gamma secretion. IL-3, IL-4 and IL-5 stimulate the growth of mucosal mast cells and eosinophils. The presence of activated T cells and eosinophils in BAL-fluid as well as increased amount of IFN-gamma and slL-2R in circulation correlate with severity of disease. Interplay between T cells and inflammatory cells through the cytokines is crucial in regulating of inflammatory processes in allergic asthma.