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ImportanceAlthough topical antibiotics are often prescribed for treating acute infective conjunctivitis in children, their efficacy is uncertain.ObjectiveTo assess the efficacy of topical antibiotic therapy for acute infective conjunctivitis.Design, Setting, and ParticipantsA randomized clinical trial was conducted in primary health care in Oulu, Finland, from October 15, 2014, to February 7, 2020. Children aged 6 months to 7 years with acute infective conjunctivitis were eligible for enrollment. The participants were followed up for 14 days. A subsequent meta-analysis included the present trial and 3 previous randomized clinical trials enrolling pediatric patients aged 1 month to 18 years with acute infective conjunctivitis.InterventionsParticipants in the present randomized clinical trial were randomized to moxifloxacin eye drops, placebo eye drops, or no intervention.Main Outcomes and MeasuresThe primary outcome in the present randomized clinical trial was time to clinical cure (in days); in the meta-analysis, the primary outcome was the proportion of participants with conjunctival symptoms on days 3 to 6.ResultsThe randomized clinical trial included 88 participants (46 [52%] girls), of whom 30 were randomized to moxifloxacin eye drops (mean [SD] age, 2.8 [1.6] years), 27 to placebo eye drops (mean [SD], age 3.0 [1.3] years), and 31 to no intervention (mean [SD] age, 3.2 [1.8] years). The time to clinical cure was significantly shorter in the moxifloxacin eye drop group than in the no intervention group (3.8 vs 5.7 days; difference, −1.9 days; 95% CI, −3.7 to −0.1 days; P = .04), while in the survival analysis both moxifloxacin and placebo eye drops significantly shortened the time to clinical cure relative to no intervention. In the meta-analysis, a total of 584 children were randomized (300 to topical antibiotics and 284 to a placebo), and the use of topical antibiotics was associated with a significant reduction in the proportion of children who had symptoms of conjunctivitis on days 3 to 6 compared with placebo eye drops (odds ratio, 0.59; 95% CI, 0.39 to 0.91).Conclusions and RelevanceIn this randomized clinical trial and systematic review and meta-analysis, topical antibiotics were associated with significantly shorter durations of conjunctival symptoms in children with acute infective conjunctivitis.Trial RegistrationClinicalTrialsRegister.eu Identifier: 2013-005623-16

Aim Our aim was to study prospectively the aetiology of neonatal conjunctivitis in a population‐based setting. Methods Altogether 173 neonates with clinical conjunctivitis aged on average 20 (SD 10) days were recruited from child welfare clinics in Oulu, Finland, in 2010–2015. Conjunctival specimens were collected from 167 neonates for multiplex polymerase chain reaction to detect 16 respiratory viruses, from 163 for polymerase chain reaction to detect Chlamydia trachomatis and Neisseria gonorrhoeae and from 160 for bacterial culture studies. The cases were followed up until the age of 18 months. Results Viral conjunctivitis was diagnosed in 8/167 (4.8%; 95% CI 2.1–9.2%), chlamydial or gonococcal conjunctivitis in 0/163 cases (0%; 95% CI 0–2.2%) and other bacterial conjunctivitis in 58/160 (36%; 95% CI 29–44%). Rhinovirus was found at the ocular site in 4/167 (2.4%) neonates, adenovirus in 3/167 (1.8%) and bocavirus in 1/167 (0.6%). The most commonly isolated bacteria included Staphylococcus aureus (16%), Moraxella catarrhalis (9.4%) and Streptococcus pneumoniae (3.1%). None of these pathogens was associated with the 4/173 (2.3%) cases later operated on for persistent nasolacrimal duct obstruction. Conclusion Chlamydia trachomatis was a rare pathogen in neonatal conjunctivitis in a population‐based setting, but respiratory viruses were detected more frequently than indicated earlier.

Objectives Chlamydia trachomatis colonisation is common in pregnant women, and it has been claimed that mother-to-child transmission may occur in 10%–70% of deliveries. C. trachomatis infections are nevertheless rarely encountered in infants in clinical practice. In order to evaluate the reason for this discrepancy, we designed a nationwide study of the C. trachomatis vertical transmission. Methods Children with a possible C. trachomatis infection were identified from two national health registries in 1996–2011. Copies of the children9s medical records were reviewed and maternal serum bank samples obtained during the index pregnancies were analysed for C. trachomatis antibodies. The risk of vertical transmission was calculated using data from two earlier studies in which nucleic acid amplification test (NAAT) positivity and seroconversion rates among women in the general population were reported. Results Altogether 206 children had a possible C. trachomatis infection, which represents 0.22 per 1000 live births (95% CI 0.19 to 0.25). The risk of vertical transmission among the estimated 24 901 NAAT-positive mothers was 0.8% (95% CI 0.7 to 0.9). Based on the annual seroconversion rate of maternal antitrachomatis antibodies, the risk of vertical transmission was 1.8% (95% CI 1.5 to 2.0). Altogether 35% of the maternal serum samples obtained in the first trimester of a pregnancy leading to a C. trachomatis infection in the infant were negative, implying that the infection was acquired during pregnancy. Conclusions C. trachomatis infections in infants were rare, with a population-based occurrence of 0.22 per 1000 live births. The risk of vertical transmission of C. trachomatis in the population was

Children with a possibleAltogether 206 children had a possible

We have observed the efficiency of antibiotic-releasing polylactide-co-glycolide (PLGA) 80/20 in preventing Staphylococcus epidermidis attachment and biofilm formation in vitro. The aim of the present study was to evaluate the effect of self-reinforced (SR) implants with enhanced antibiotic release on bacterial attachment and biofilm formation rates, and also on growth inhibition of Staphylococcus epidermidis. Cylindrical SR-PLGA+AB specimens (length 30 mm, diameter 3 mm) were examined by scanning electron microscopy (SEM) for attachment of S. epidermidis ATCC 35989 on biomaterial surface and formation of biofilm, after incubating with bacterial suspension of ca. 105 cfu/mL for 1, 3, 7, 14 and 21 days. SR-PLGA and SR-PLGA+AB implants were tested on agar plates by measuring the inhibition distance around implants. On the surface of SR-PLGA+AB, at days 1, 3, 7, 14 and 21, the percentage of areas with not a single bacteria attached, was 88.6%, 71.1%, 73.7%, 73.7%, and 68.4%, respectively. On the areas where bacteria were detected, the number of bacterial cells remained low during whole study period, and no significant increase by time was seen. There was no biofilm observed on 97-99% of the examined areas during the whole study period on SR-PLGA+AB. In agar plates, the SR-PLGA+AB showed inhibition of bacterial growth, with (mean) 53.2 mm diameter of inhibition area with peeled implants and 50.5 mm with non-peeled implants. There was no inhibition seen around implants without ciprofloxacin. Bioabsorbable ciprofloxacin-releasing self-reinforced PLGA (SR-PLGA+AB) was superior to plain SR-PLGA in preventing bacterial attachment, biofilm formation, and also the growth of Staphylococcus epidermidis.

Objectives Xylitol is a sugar alcohol which reduces the growth of Streptococcus pneumoniae and the adherence of pneumococci and Haemophilus influenzae to nasopharyngeal cells. Xylitol prevents acute otitis media but does not decrease nasopharyngeal carriage of pneumococci. We hypothesized that xylitol could affect the surface structures of viable pneumococci, which would further explain the mechanism of action of xylitol in preventing acute otitis media. Methods We exposed five strains of pneumococci to 0.5%-5% xylitol, 5% glucose, 5% fructose and 5% sorbitol or control medium (brain heart infusion) for 0.5-2 h and examined the ultrastructure of bacteria by electron microscopy. Results The cell wall of pneumococci became more diffuse, the polysaccharide capsule became ragged and the proportion of damaged pneumococci increased after exposure to xylitol for 2 h, but not after exposure to other sugars or control medium. The phenotype of all pneumococcal strains was opaque before xylitol exposure and became almost transparent both in xylitol and in control medium during the experiment. Conclusions This study demonstrates further that xylitol has a harmful effect on pneumococci. The observed changes in the polysaccharide capsule and the cell wall of pneumococci could affect the adherence and virulence of pneumococci, explaining the good clinical efficacy of xylitol in the prevention of acute otitis media.

Persistent human papillomavirus (HPV) infection is an established cause of cervical cancer, but the role of other sexually transmitted agents, most notably Chlamydia trachomatis, has not been well defined. The women participating in the population-based cervical cancer screening program in Vasterbotten county of Northern Sweden were followed up for up to 26 years to identify 118 women who developed cervical cancer after having had a normal Pap smear (on average 5.6 years later; range 0.5 months-26 years). As controls, we selected another 118 women who were matched by birth cohort, time-point of sampling of the baseline normal smear and who had a normal smear at the time when the corresponding case was diagnosed with cancer. The Pap smears and cervical cancer biopsies were analyzed by PCR for C. trachomatis DNA and for HPV DNA. At baseline, C. trachomatis DNA was present in 8% of cases but not among any one of the controls. The relative risk for cervical cancer associated with past C. trachomatis infection, adjusted for concomitant HPV DNA positivity, was 17.1 (95% CI 2.6-infinity). The presence of C. trachomatis and of HPV were not interrelated. Whereas C. trachomatis was primarily found in specimens taken many years before cancer diagnosis, HPV DNA was associated with a short lag time before cancer diagnosis. Whereas most women who were HPV DNA-positive in the prediagnostic smear were also positive for the same virus in the cervical cancer biopsy, none of the women were positive for C. trachomatis in both the prediagnostic smear and in the subsequent cervical cancer. In conclusion, a prior cervical C. trachomatis infection was associated with an increased risk for development of invasive cervical cancer.

Keratinocytes of psoriatic skin show aberrant expression of membrane-bound CD14 (mCD14). In addition, soluble CD14 (sCD14) is elevated in the sera of psoriatic patients. The mechanisms leading to increased CD14 expression and secretion in psoriasis are poorly understood. A bi-allelic polymorphism in the promoter region of the CD14 gene controls CD14 expression on monocytes and sCD14 levels in the sera of healthy subjects. In this context, we explored the CD14 promoter region genotypes of 63 Finnish patients with psoriasis and 126 non-psoriatic controls using a new ARMS-PCR method. No differences in the CD14 genotype frequencies were found between the groups. Thus, our results suggest that the enhanced CD14 expression in psoriasis is not attributable to functional variants of CD14 (-159C/T).

Xylitol is effective in preventing acute otitis media by inhibiting the growth of Streptococcus pneumoniae . To clarify this inhibition we used fructose, which is known to block similar growth inhibition observed in Streptococcus mutans . In addition, we evaluated the efficacy of sorbitol in inhibiting the growth of pneumococci, as sorbitol is widely used for indications similar to those for which xylitol is used. The addition of 5% xylitol to the growth medium resulted in marked growth inhibition, an effect which was totally eliminated in the presence of 1, 2.5, or 5% fructose but not in the presence of 1 or 5% glucose, 1% galactose, or 1% sucrose. This finding implies that xylitol-induced inhibition of pneumococcal growth is mediated via the fructose phosphotransferase system in a way similar to that in which mutans group streptococcal growth is inhibited. The addition of sorbitol at concentrations of 1, 2.5, or 5% to the growth medium did not affect the growth of pneumococci and neither inhibited nor enhanced the xylitol-induced growth impairment. Thus, it seems that xylitol is the only commercially used sugar substitute proven to have an antimicrobial effect on pneumococci.

The in vitro susceptibility of 38 strains of Francisella tularensis (biovar F. tularensis palaearctica) was determined using Etests on cysteine heart agar plates with 2% haemoglobin. All strains were susceptible to the antibiotics traditionally used to treat tularaemia, such as streptomycin (MIC(90) 4.0 mg/L), tetracycline (MIC(90) 0.38 mg/L) and chloramphenicol (MIC(90) 0.38 mg/L), and to aminoglycosides, such as tobramycin (MIC(90) 1.5 mg/L) and gentamicin (MIC(90) 1.0 mg/L). The quinolones examined had low MIC(90)s: ciprofloxacin, 0.016 mg/L; levofloxacin, 0.016 mg/L; grepafloxacin, 0.047 mg/L; and trovafloxacin, 0.032 mg/L. In contrast, all the strains were resistant to beta-lactams and azithromycin. Quinolones thus seem to be promising drugs for the treatment of tularaemia.

Psoriasis vulgaris is a chronic skin disease with a genetic and immunological background. We have previously defined the two most frequent risk haplotypes in Finns: A2,B13,Cw6,DR7,DQA1*0201 and A1,B17,Cw6,DR7,DQA1*0201. The aim of this study was to further examine whether the flanking regions, URRs of DQ (QAP and QBP) and TAP1 and TAP2 genes are involved in susceptibility to psoriasis. The frequency of QAP2.1 was increased in psoriatics as compared with controls ( P c = 3.6 × 10 –2 , RR = 5.0), and the frequency of QAP4.1 was decreased in psoriasis patients ( P c = 4.2 × 10 –2 ). The frequency of the phenotype combination Val/Ile at position 379 of TAP2 was decreased in patients ( P c = 1 × 10 –2 ). The allele and phenotype frequencies of TAP1 and TAP2 genes were not different between these groups. Haplotypes A2, B13,Cw6,DR7,DQA1*0201,QAP2.1 and A1,B17,Cw6, DR7,DQA1*0201,QAP2.1 are the two most frequent HLA marker haplotypes for psoriasis vulgaris in Finns, Cw6, DR7, DQA1*0201 and QAP2.1 being the most important single alleles for the risk of this disease.

We wanted to investigate whether rheumatoid arthritis (RA) patients, defined by the American College of Rheumatology (ACR) 1987 criteria and selected from one community by the help of the official Finnish data registers, share the common HLA susceptibility genes. The HLA frequencies of 88 RA patients representing 85% of the prevalent cases of RA in the community were compared with those of 188 healthy controls. Fifty-four per cent of the index cases with RA had DR4 compared with 30% of the healthy controls (P0.001). The 'RA susceptibility sequence' was found in 75% of the DRB1 genes in the index cases, but it did not correlate with the severity of the disease. The frequency of DR3 was not increased in RA patients but it was associated with features of severe disease, that is, with a high erythrocyte sedimentation rate (P0.05), extra-articular disease (P0.01) and prostheses in large joints (P0.05). According to our results community-based RA patients satisfying the new ACR criteria show the common DR4 association. DR3 was the only HLA allele which showed some disease-modifying effect correlating with the severity of RA.

It has been suggested that biofilm formation by uropathogenic Escherichia coli (UPEC) isolates is associated with recurrence and persistence of urinary tract infection (UTI). We compared the in vitro biofilm formation of UPEC isolates from children with acute or recurrent UTI. Employing 206 consecutive clinical UPEC isolates from children with proven UTI, i.e., pyelonephritis (n = 78), recurrent pyelonephritis (n = 10), cystitis (n = 84) or recurrent cystitis (n = 34), we applied 1 % crystal violet staining to polystyrene microtitre plates at 72 h and measured the optical density (OD) values. The method had been validated to measure biofilm formation against confocal laser scanning microscopy and scanning electron microscopy. The OD values were lower in the recurrent cystitis group than in the other groups (mean OD 0.36, SD 0.21 vs mean 0.47, SD 0.36, P = 0.04) and higher in the recurrent pyelonephritis group than in the other groups (mean OD 0.69, SD 0.33 vs mean OD 0.44, SD 0.34, P = 0.006) indicating biofilm formation of strains causing recurrent pyelonephritis. It appears that the properties of UPEC isolates required for effective biofilm growth on an abiotic surface are important for recurrent pyelonephritis, but not for recurrent cystitis. It would be valuable in the future to analyze whether the biofilm properties of E. coli observed in vitro predict a slower clinical response to antimicrobial treatment and increased renal scar formation after UTI.

The extreme polymorphism of HLA genes makes them a powerful tool for distinguishing between different genetic populations. Five-locus HLA haplotypes of Finns (from Oulu, Northern Finland) are described here in order to characterize further the migration pathways of the population to Finland after the Ice Age. From random families, 364 haplotypes were obtained. The most frequent Finnish haplotype A3,Cw4,B35,DR1,DQ1 (7.7%) is a Caucasoid ancestral haplotype and is shared with Italians of Celtic and non-Celtic origin. The haplotype A1,Cw7,B8,DR3,DQ2, which occurs in 4.7% of Finns, is the most frequent haplotype in Caucasoids. The haplotypes A3,Cw7,B7,DR2,DQ1 (3.6%) and A2,Cw7,B7,DR2,DQ1 (2.5%) are shared with several Caucasoid populations and the latter also with Jamaican blacks. A2,Cw5,B44,DR5,DQ3 (0.8%) is shared with Italians of Celtic and non-Celtic origin, A2,Cw6,B13,DR7,DQ2 (1.1%) with Caucasoids in the USA and A9,Cw4,B35,DR1,DQ1 (0.8%) with Mongoloids. The haplotypes A2,CW3,B62,DR4,DQ3 (3.0%), A2,Cw2,B27,DR8,DQ4 (1.7%), A2,Cw3,B62,DR6,DQ1 (1.4%) and A2,Cw1,B27,DR4,DQ3 (1.4%) were also found to be among the most frequent in the Finnish population. The most frequent HLA haplotypes are consistent with the postulated ancient migration of populations from southern Scandinavia and Germany to Finland, the most frequent haplotype suggesting a common Celtic origin and one less frequent haplotype suggesting an influence from the east.

The gene region on chromosome 11p15.5 known to be involved in insulin-dependent diabetes mellitus (IDDM) susceptibility was recently mapped to a 4.1-kilobase region including the insulin gene. The region contains 10 candidate polymorphisms that are in strong linkage disequilibrium. By genotyping 7 of these 10 polymorphisms and the tyrosine hydroxylase microsatellite in Finnish Caucasoid IDDM patients and control subjects, we demonstrate that many of the polymorphisms found to be associated with IDDM in other Caucasoid populations do not show any association in this Finnish population. Of the polymorphisms typed, only those at –23 Hph I and the variable number of tandem repeats (VNTR) sites confer significant relative risk. Furthermore, we have demonstrated that the –23 Hph I polymorphism cannot explain the association. Comparison of the genotypic patterns observed here and previously suggests that the VNTR is the most likely candidate for IDDM2. The VNTR is located adjacent to defined regulatory DNA sequences affecting insulin gene expression, which suggests a possible effect on expression of insulin or one of the neighboring genes, tyrosine hydroxylase or insulin-like growth factor 2.

Mixed connective tissue disease (MCTD) and systemic lupus erythematosus (SLE) are autoimmune diseases with a genetic background, and it is reasonable to suggest that aberrations in T cell receptor (TCR) genes could contribute to these diseases, as they play an important role in immune regulation. We studied TCR beta-chain gene segments V beta 8, V beta 11 and C beta with restriction fragment length polymorphism (RFLP) in MCTD and SLE patients and controls. Haplotypes could be assigned in individuals who were homozygous for two or three of these three loci, whereupon the haplotype 2/25/10 (V beta 8/V beta 11/C beta) was found to be under-represented in MCTD (P = 0.029). The frequencies of individual alleles in both groups were similar to those of the controls, whereas the number of homozygotes within V beta 8 gene (23/23 kb and 2/2 kb) was increased in MCTD (P = 0.028). It is concluded that the distribution of TCR beta-chain genes could be aberrant in MCTD and could play a role in susceptibility, whereas the TCR beta-chain gene distribution in the SLE patients did not differ from that of the controls.

Tapiainen T, Kujala T, Kaijalainen T, Ikaheimo I, Saukkoriipi A, Renko M, Salo J, Leinonen M, Uhari M. Biofilm formation by Streptococcus pneumoniae isolates from paediatric patients. APMIS 2010; 118: 255–60. The clinical significance of pneumococcal biofilm formation is largely unknown. To clarify this, we tested whether the ability of pneumococcal clinical isolates to form biofilm in vitro accounts for the diverse clinical outcomes. Clinical pneumococcal isolates were cultured from the nasopharynx (n = 106), middle ear effusion (n = 43) and blood (n = 55) of 204 children altogether. Biofilm formation, assessed by measuring optical density (OD) values in microtitre plates after crystal violet staining, did not differ between the bacteria from different sources (p = 0.18), the mean OD values of the isolates being 0.119 [95% confidence interval (CI) 0.100–0.138] in the nasopharynx samples, 0.094 (95% CI 0.069–0.119) in the acute otitis media cases, 0.109 (95% CI 0.077–0.141) in the secretory otitis media cases, 0.122 (95% CI 0.084–0.160) in those with sepsis and 0.175 (95% CI 0.071–0.280) in those with other invasive infections. Serotypes 33 and 14 were the most efficient in forming biofilms, whereas serotypes 3 and 38 were poor biofilm producers. We conclude that the clinical presentation of pneumococcal disease did not differ in relation to biofilm formation in vitro, even though there was marked variation between the clinical isolates and serotypes.

Nickel is the major cause of metal-induced contact allergy. To understand the mechanism of its immune reaction, we studied changes in lymphocyte surface markers during nickel challenge in both allergic and healthy subjects using an in vitro nickel reaction in which the lymphocytes of allergic subjects divide when they are stimulated with nickel sulfate. The lymphocytes were labeled with monoclonal antibodies (MAbs) to cell-surface antigens and studied by flow cytometry. Mononuclear cells from the nickel reaction in vivo were studied from skin biopsy specimens using MAbs and avidin-biotin immunohistochemistry. Nickel-induced lymphoblast transformation occurred in vitro only in cells from nickel-allergic subjects. CD4 + cells and CD45RO + cells were overrepresented among the lymphoblasts of nickel-sensitive subjects, whereas CD8 + and CD8 + CD11b + and CD4 + CD45R + cells were underrepresented. The lymphoblasts contained T cells with the following activation markers: CD25, HLA-DR, CD26, CD71, Ki-67, and activation-associated antigen detected by the MAb, M21C5, but they were CD30 + . CD16 + cells were overrepresented among the lymphoblasts. Nickel-reacting T cells used predominantly the T cell receptor, αβ-heterodimer, but no preferential selection of either Vβ5, Vβ6, or Vβ8 was observed. The phenotypes of nickel-reacting cells from cutaneous biopsy specimens were in agreement with the in vitro results.

Recent reports suggest that the HLA-DQA1 gene may be important in determining susceptibility to and outcome of Helicobacter pylori infection. To determine if there is an association between HLA-DQA1 alleles and H. pylori antibodies, DQA1 alleles and H. pylori-specific antibodies were determined in 199 random subjects of Finnish origin (mean age 43 years, range 22-69 years). H. pylori-specific class IgG antibodies were measured using the EIA method (Pyloriset-EIA-G, Orion Diagnostica, Espoo, Finland). HLA-DQA1 typing was carried out using PCR-SSP (PCR with sequence-specific primers). There were 64 subjects with H. pylori-specific class IgG antibodies (ab+) and 135 subjects without H. pylori-specific class IgG antibodies (ab-). Gene and phenotype frequencies of HLA-DQA1 alleles were similar in the ab+ and ab- subjects (P = NS). The data suggest that no single HLA-DQA1 allele is associated with the presence of serum antibodies against H. pylori.

Background Candida krusei infections are associated with high mortality. In order to explore ways to prevent these infections, we investigated potential routes for nosocomial spread and possible clonality of C. krusei in a haematological unit which had experienced an unusually high incidence of cases. Methods We searched for C. krusei contamination of the hospital environment and determined the level of colonization in patients and health care workers. We also analyzed the possible association between exposure to prophylactic antifungals or chemotherapeutic agents and occurrence of C. krusei. The C. krusei isolates found were genotyped by pulsed-field electrophoresis method in order to determine possible relatedness of the cases. Results Twelve patients with invasive C. krusei infection and ten patients with potentially significant infection or mucosal colonization were documented within nine months. We were unable to identify any exogenic source of infection or colonization. Genetic analysis of the isolates showed little evidence of clonal transmission of C. krusei strains between the patients. Instead, each patient was colonized or infected by several different closely related genotypes. No association between medications and occurrence of C. krusei was found. Conclusion Little evidence of nosocomial spread of a single C. krusei clone was found. The outbreak may have been controlled by cessation of prophylactic antifungals and by intensifying infection control measures, e.g. hand hygiene and cohorting of the patients, although no clear association with these factors was demonstrated.

Antibiotic coating systems have been successfully used to prevent bacterial attachment and biofilm formation. Our purpose was to evaluate whether bioabsorbable polylactide-co-glycolide (PLGA) 80/20 on its own, and PLGA together with ciprofloxacin (PLGA+C) have any advantages over titanium in preventing Staphylococcus epidermidis attachment and biofilm formation in vitro. Cylindrical specimens of titanium, PLGA, and PLGA+C in triplicate were examined for S. epidermidis ATCC 35989 attachment and biofilm formation after incubation with a bacterial suspension of about 105 cfu/mL for 1, 3, 7, 14, and 21 days, using scanning electron microscopy. Growth inhibition properties of PLGA and PLGA+C cylinders were tested on agar plates. On days 1, 3, and 21, no bacterial attachment was seen in 19.5, 9.2, and 41.4% of the titanium specimens; in 18.4, 28.7, and 34.5% of the PLGA specimens; and in 57.5, 62.1, and 57.5% of the PLGA+C specimens, respectively. During the whole study period, no biofilm was observed on 74–93% of the titanium specimens, 58–78% of the PLGA specimens, and 93–100% of the PLGA+C specimens. PLGA+C showed clear bacterial growth inhibition on agar plates, while PLGA and titanium did not show any inhibition. PLGA+C bioabsorbable material was superior to titanium in preventing bacterial attachment and biofilm formation and may have clinical applicability, for example, in prevention of infection in trauma surgery or in the treatment of chronic osteomyelitis. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006

A 56-year-old male was admitted to the hospital after a bear attack. A wounded brown bear ( Ursus arctos ) had attacked the patient. The patient had several bite wounds. The most serious wound was a deep penetrating bite wound in his left thigh. This wound needed immediate debridement, and

Persistent human papillomavirus (HPV) infection is an established cause of cervical cancer, but the role of other sexually transmitted agents, most notably Chlamydia trachomatis, has not been well defined. The women participating in the population-based cervical cancer screening program in Västerbotten county of Northern Sweden were followed up for up to 26 years to identify 118 women who developed cervical cancer after having had a normal Pap smear (on average 5.6 years later; range 0.5 months-26 years). As controls, we selected another 118 women who were matched by birth cohort, time-point of sampling of the baseline normal smear and who had a normal smear at the time when the corresponding case was diagnosed with cancer. The Pap smears and cervical cancer biopsies were analyzed by PCR for C. trachomatis DNA and for HPV DNA. At baseline, C. trachomatis DNA was present in 8% of cases but not among any one of the controls. The relative risk for cervical cancer associated with past C. trachomatis infection, adjusted for concomitant HPV DNA positivity, was 17.1 (95% CI 2.6-infinity). The presence of C. trachomatis and of HPV were not interrelated. Whereas C. trachomatis was primarily found in specimens taken many years before cancer diagnosis, HPV DNA was associated with a short lag time before cancer diagnosis. Whereas most women who were HPV DNA-positive in the prediagnostic smear were also positive for the same virus in the cervical cancer biopsy, none of the women were positive for C. trachomatis in both the prediagnostic smear and in the subsequent cervical cancer. In conclusion, a prior cervical C. trachomatis infection was associated with an increased risk for development of invasive cervical cancer.

Since an association has been reported between nickel allergy and HLA-DQA TaqI restriction fragment length polymorphism, we typed the DQA1 locus by a more precise method to confirm the association and characterize it better. Typing was extended to the DQB1 locus. The loci were typed using polymerase chain reaction and sequence-specific oligonucleotides. The DQA1 allele 0601 was slightly overrepresented among the patients, but the p value was not significant. The frequencies of DQB1 locus alleles did not differ from those of the controls. Thus we were unable to confirm any association between HLA and nickel allergy.

The aim of the study was to assess the prevalence of rheumatoid factor (RF) in a community-based rheumatoid arthritis (RA) series. The subjects of the series represented prevalent RA cases in the Kuusamo community in Northern Finland with 13,000 adult inhabitants. The patients were selected from the official Finnish data registers and from among the subjects who had consulted the local general practitioners due to rheumatic complaints in the recent years, using the American Rheumatism Association (ARA) 1987 classification criteria for inclusion. For this study, ninety-five out of the 103 RA patients so found were RF-tested by immunoturbidimetry. At the time of the study. 71 (75%) of the 95 cases were RF positive, 83 (87%) being 'ever' positive (in one case the early RF status was unclear). Our result contrasts with the much lower prevalence figures (25-60%) obtained from the earlier cross-sectional population-based RA studies, which have used the ARA 1958 definite RA as the inclusion criterion of the subjects. All the eleven patients with RF-negative RA had erosive joint disease. The RF-negative RA patients had a significantly lower frequency of HLA-DR4 (18%) than the RF-positive ones (58%), p < 0.05. We found a high frequency of RF among prevalent community-based RA cases meeting the ARA criteria. According to our results, RF-negative non-erosive RA is very rare among cases selected with the above methods.

Nickel allergy is manifested as contact allergic eczema elicited by delayed-type hypersensitivity, the reaction being mediated by T lymphocytes. We examined the T-cell receptor (TCR) beta-chain variable gene segment (Vbeta) use of nickel-induced CD4+ and CD8+ T cells in the peripheral blood of nickel-sensitive and nonsensitized subjects. The results show that each patient had an individual Vbeta repertoire overexpressed, these being in CD4+ cells Vbeta10 and Vbeta13 (in subject A); Vbeta1, Vbeta2, Vbeta13 and Vbeta21 (subject B); Vbeta1 and Vbeta10 (subject C); Vbeta9 and Vbeta19 (subject D). Thus, no single Vbeta gene dominated in a majority of the CD4+ samples. The Vbeta genes overexpressed in patient CD8+ nickel-induced T cells were Vbeta1 (in subject A), Vbeta1 (subject B), Vbeta1 and Vbeta2 (subject C) and Vbeta7 (subject D), domination of Vbeta1 being seen in most of the CD8+ samples (75%). No specific overexpression of any Vbeta genes in the nickel-allergic subjects was found in comparison with the non-sensitized subjects. In conclusion, an individual pattern of restricted Vbeta genes was induced with nickel in CD4+ and CD8+ T cells in each nickel allergy patient.

Psoriasis vulgaris has HLA associations. We have previously defined HLA-Cw6,DR7,DQA1*0201 as the central element of the risk haplotypes for psoriasis. On the other hand, Cw6 as a single gene has the strongest association with psoriasis. The aim of this study was to determine whether the risk haplotype and Cw6 correlate with the clinical parameters of the disease. The series consisted of 64 patients and the clinical parameters were age at onset, family history of psoriasis, arthritis and the frequency of inpatient treatment. The HLA risk haplotype Cw6,DR7,DQA1*0201 had previously been found in 30% and Cw6 alone in 54% of the patients. The presence of Cw6 correlated with early age at onset (Pc = 0.01). The presence of the risk haplotype correlated with a positive family history of psoriasis among the first-degree relatives (Pc = 0.02) and an overall positive family history (Pc = 0.04), but Cw6 had a stronger correlation with an overall positive family history (Pc = 0.01). There were no positive correlations with arthritis or the number of inpatient treatment periods. Only type I psoriasis was associated with Cw6 (Pc = 0.0006). In conclusion, Cw6 and the haplotype Cw6,DR7,DQA1*0201 are important in the heredity of psoriasis vulgaris, but the presence of Cw6 alone is sufficient to indicate a clinically significant risk for psoriasis.

The polymorphism of the HLA-G gene can be identified by PCR-RFLP analysis. This short communication describes the PCR-RFLP analysis of HLA-G polymorphisms in exons 2 and 3 and the association of different HLA-G and HLA-A alleles in 26 healthy Finnish families.

Psoriasis vulgaris is a skin disease with an immunological and genetic background present in 1-3% of the population. We studied the genetic susceptibility to psoriasis vulgaris in Finns with serological HLA typing and genomic HLA class II typing of the DQ and DP loci to evaluate the risk of developing psoriasis. The haplotypes most frequently distinguishing between psoriatics and controls were those that carried Cw6 (P10(-8)), DQA1*0201 (P = 9.3 x 10(-6)) and DR7 (P = 3.9 x 10(-5)). The two most frequent marker haplotypes were A2,B13,Cw6,DR7, DQA1*0201 and A1,B17,Cw6,DR7,DQA1*0201, which were not found among the control subjects. A deficit of haplotype B8,DR3,DQ2 (2 out of 124 in the patients versus 15 out of 106 in the controls, P = 1.5 x 10(-4)) was found, and this was in accordance with a slightly decreased frequency of DQA1*0501 (P = 3.1 x 10(-2)), which was usually linked with this haplotype. These results stimulate the research for a genetic resistance factor in psoriasis. Thus, this report sheds further light on the immunogenetic background of psoriasis in Finland. We conclude that the inheritance of psoriasis has a polygenic mode, in which the Cw6,DR7,DQA1*0201 combination seems to be important (P = 7.5 x 10(-7), relative risk 24.4, aetiological factor 0.29).

A close association was found between a specific sequence of HLA-C and psoriasis vulgaris in Finnish patients (chi 2 = 18.4, P = 1.78 x 10(-5)). This sequence codes for alanine at position 73 of the HLA-C molecule in the antigen binding cleft, and alanine may play a role in susceptibility to the disease.

SUMMARY Expression of the erythrocyte complement receptor (C3bR = CR1 = CD35) and its genomic polymorphism (HindIII RFLP) was studied in a group of 80 patients with IDDM, 31 healthy siblings and 101 healthy blood donors. Defective CR1 expression was found in 26% of the patients with IDDM compared with 9% of the controls (P

ContextHuman papillomavirus (HPV) infection has been established as a cause of cervical cancer. Epidemiologic studies suggest that Chlamydia trachomatis infection also confers increased risk for cervical squamous cell carcinoma (SCC). Whether this risk is serotype-specific is unknown.ObjectiveTo study the association between exposure to different C trachomatis serotypes and subsequent development of cervical SCC.Design and SettingLongitudinal, nested case-control study within a cohort of 530 000 women who provided samples to serum banks in Finland, Norway, and Sweden. The data files were linked to respective national cancer registries.SubjectsOne hundred twenty-eight women who had developed invasive cervical SCC at least 12 months following serum donation. Each case had 3 matched controls.Main Outcome MeasureRisk for the development of cervical SCC by IgG antibodies to 10 different C trachomatis serotypes, adjusted for antibodies to HPV types 16, 18, and 33 and for serum cotinine levels.ResultsOf specific C trachomatis serotypes, serotype G was most strongly associated with SCC (adjusted odds ratio [OR], 6.6; 95% confidence interval [CI], 1.6-27.0). Other serotypes associated with SCC were I (OR, 3.8; 95% CI, 1.3-11.0) and D (OR, 2.7; 95% CI, 1.3-5.6). Presence of serum IgG antibodies to more than 1 serotype increased the adjusted ORs for SCC (P

The influx of [14C]isethionate (ISA) into rat brain slices was studied with and without taurine. This influx was relatively rapid, but took place largely by a non-saturable, passive mechanism, which transferred much less ISA into the brain cells than taurine. Taurine inhibited the influx of ISA competitively (Km=50 and 100 μmol/l) at low ISA concentrations, and ISA that of taurine non-competitively (V=200 and 400–700 μmol×min−1×kg−1 wet weight) at high taurine concentrations. It thus appears that ISA and taurine may have a small number of common transport sites at brain cell membranes, but these are apparently of little significance for the total transport of ISA.