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Rudder systems (rudder control surfaces and steering gear) are a safety critical element of ships operating in ice-covered waters. Icebreaking ships equipped with single rudders are particularly vulnerable considering the remote and often isolated locations in which they operate. The IACS Polar Class Rules were developed as a set of harmonized requirements for ships operating in polar waters. First published in 2006 the rules contain requirements for dimensioning the hull structure and propulsion machinery to resist ice loads. There are however no specific requirements for rudders — the rules simply require appendages to be dimensioned using the hull ice load. This paper presents a series of studies aimed at providing guidance on dimensioning rudders and steering gear systems for operation in ice. Using existing ship reference cases and rudder ice loading scenarios found in previous rules and guidelines a simplified set of design approaches are presented. These approaches are evaluated with Finite Element Analysis and compared with selected measured full-scale data and damage incidents. Guidance is provided on system protection mechanisms for the steering gear under these design and over-load cases. In addition, a comparison is made between the results and those derived from using the hull area design pressures in the current IACS rules.

Currently there is extensive knowledge on many aspects of mold-related disease, but dampness and mold hypersensitivity syndrome (DMHS) is a broader definition than mold-related disease. It comprises seemingly nonrelated sequelae that however are all influenced by an exposure to dampness microbiota. In exposed individuals these diseases occur far more often than purely by chance. DMHS is related to some extent to environmental intolerances, such as multiple chemical sensitivity (MCS) and electromagnetic (EMS). The aim of this review is to highlight the association of DMHS with intolerances to many environmental factors, such as autoimmunity, chronic fatigue syndrome (CFS) and cancer. A variety of underlying mechanisms are involved that are not presented here. With this communication we want to challenge the attitudes and share our clinical experience.

In the IACS Polar Class Rules, primary structures are required to be assessed with direct calculation methods, which in most cases is either linear or non-linear finite element analysis. For linear analysis a clear set of requirements and acceptance criteria are provided in the rules. This approach is currently the most widely used assessment method although non-linear analysis would provide better insight into the behavior of the structure, giving designers tools to reduce weight and/or improve safety. The current rule requirements for non-linear analysis are high-level in nature and not easily applicable to practical design work. In order to implement non-linear analysis practically, a simple-to-use acceptance criteria is be needed. In this paper, a robust and simple-to-use assessment methodology and acceptance criteria is proposed. The proposed method provides means to ensure proper structural hierarchy. Appropriate safety margins are described through the plastic response of the local frame and the primary structural member. Allowable plastic deformation caused by the design ice load is determined by relating the permanent set of the structure to newbuild vessel production tolerances. An example analysis comparing the proposed method to existing linear and non-linear methods is presented. The proposed method ensures that the structure remains serviceable throughout the lifetime of the vessel.

The Polar Class Module Carriers AUDAX and PUGNAX were built for a unique service; year-round transportation of ultra-heavy construction modules for the Yamal LNG plant which is located near Sabetta on the Yamal Peninsula, 4 degrees north of the Arctic Circle. The average- and winter conditions in the Russian Arctic, especially the Ob Bay area, are extremely harsh. Dedicated Vessels were essential to provide the Client the required year-round module transportation service in these challenging conditions. The unique design of the sister vessels AUDAX and PUGNAX is jointly developed by Aker Arctic Technology and RED BOX Energy Services. A special custom/one-off hull shape has been engineered to ensure the Vessels can perform reliable module transportation in Arctic conditions within a limited timeframe. The requirement for stern-to loadout and discharge operations made a conventional hull shape or double acting ships (sailing a-stern in ice) design impossible. With the aid of CFD calculations and model testing at Aker Arctic's own test basin, the unique hull shape for the Vessels was developed. With the CFD analysis a new ice bow was designed specifying icebreaking capacities to 1.5 meters of level ice. Results of the performed tests demonstrated the Vessels design exceed the minimum required performance. Furthermore, in close cooperation with DNV-GL the Vessels obtained Polar Class 3 (PC-3) approval. In addition, two special studies were done by DNV-GL and the CNIIMF to proof compliance with ARC-7 Class, the Russian equivalence of PC-3. The bow design of the 43 meter (141 foot) wide Vessels enables them to break ice up to 1.5 meters (5 foot) thick, independently. AUDAX and PUGNAX can cope with temperatures of -50°C (-58°F) and still navigate safe and reliable during the 9-months ice coverage period in the Arctic, including the challenging polar nights which last for two months annually. Both Vessels were delivered early 2016 and have, since then, profoundly navigated around the clock; AUDAX and PUGNAX delivered 48 modules at the Yamal Peninsula while safe navigating 30.000 mile through ice covered waters. In March 2017, Aker Arctic and RED BOX jointly assessed the performance of AUDAX, when the Vessel sailed from the Yamal Peninsula to Zeebrugge (Belgium). The overall performance of the AUDAX was impressive, performing well-above its specifications in both ice breaking conditions as well as in modules loading- and discharge operations. AUDAX and PUGNAX are one of the largest icebreaking Vessels in the world. Combining these icebreaking capabilities with a unique module transportation approach, RED BOX created an extraordinary Logistic Service to serve large-scale Energy Infrastructure projects in Arctic Regions. The additional special features of the Vessels which includes deck heating and internal ballast transfer make efficient transportation and cargo operations in extreme harsh environments feasible.

Introduction Homozygous deficiencies of complement C4A or C4B are detected in 1-10% of populations. In genome-wide association studies C4 deficiencies are missed because the genetic variation of C4 is complex. There are no studies where the clinical presentation of these patients is analyzed. This study was aimed to characterize the clinical features of patients with homozygous C4A or C4B deficiency. Material and methods Thirty-two patients with no functional C4A, 87 patients with no C4B and 120 with normal amount of C4 genes were included. C4A and C4B numbers were assessed with genomic quantitative real-time PCR. Medical history was studied retrospectively from patients' files. Results Novel associations between homozygous C4A deficiency and lymphoma, coeliac disease and sarcoidosis were detected. These conditions were present in 12.5%, (4/32 in patients vs. 0.8%, 1/120, in controls, OR = 17.00, 95%Cl = 1.83-158.04, p = 0.007), 12.5% (4/32 in patients vs. 0%, 0/120 in controls, OR = 1.14, 95%Cl = 1.00-1.30, p = 0.002) and 12.5%, respectively (4/32 in patients vs. 2.5%, 3/120 in controls, OR = 5.571, 95%Cl = 1.79-2.32, p = 0.036). In addition, C4A and C4B deficiencies were both associated with adverse drug reactions leading to drug discontinuation (34.4%, 11/32 in C4A-deficient patients vs. 14.2%, 17/120 in controls, OR = 3.174, 95%Cl = 1.30-7.74, p = 0.009 and 28.7%, 25/87 in C4B-deficient patients, OR = 2.44, 95%Cl = 1.22-4.88, p = 0.010). Conclusion This reported cohort of homozygous deficiencies of C4A or C4B suggests that C4 deficiencies may have various unrecorded disease associations. C4 gene should be considered as a candidate gene in studying these selected disease associations.

We compared the clinical findings and survival in patients with Mycobacterium avium complex (MAC) and other non-tuberculous mycobacteria (NTM). A total of 167 adult non-human immunodeficiency virus (HIV) patients with at least one positive culture for NTM were included. Medical records were reviewed. The patients were categorised according to the 2007 American Thoracic Society (ATS) criteria. MAC comprised 59 % of all NTM findings. MAC patients were more often female (70 % vs. 34 %, p

A great variety of non-specific symptoms may occur in patients living or working in moisture-damaged buildings. In the beginning, these symptoms are usually reversible, mild, and present irritation of mucosa and increased morbidity due to respiratory tract infections and asthma-like symptoms. Later, the disease may become chronic and a patient is referred to a doctor where the assessment of dampness and mold hypersensitivity syndrome (DMHS) often presents diagnostic challenges. Currently, unanimously accepted laboratory tests are not yet available. Therefore, the diagnosis of DMHS is clinical and is based on the patient’s history and careful examination. In this publication, I reviewed contemporary knowledge on clinical presentations, laboratory methods, and clinical assessment of DMHS. From the literature, I have not found any proposed diagnostic clinical criteria. Therefore, I propose five clinical criteria to diagnose DMHS: (1) the history of mold exposure in water-damaged buildings, (2) increased morbidity to due infections, (3) sick building syndrome, (4) multiple chemical sensitivity, and (5) enhanced scent sensitivity. If all the five criteria are met, the patient has a very probable DMHS. To resolve the current problems in assigning correct DMHS diagnosis, we also need novel assays to estimate potential risks of developing DMHS.

In this paper, the relationship between the rudder lift force and ice loads on the stern shoulder of a vessel hull is studied. The study is based on full-scale measurements with research vessel SA Agulhas II on Antarctic voyage 2012-2013. The results show that rudder lift force has a significant effect on the ice loads on the stern shoulder region.

Non-tuberculous mycobacteria (NTM) cause disease in healthy and immunocompromised patients. The American Thoracic Society (ATS) 2007 diagnostic criteria were devised to distinguish NTM disease from airway colonization. The aim of this study was to evaluate the prognostic value of the ATS criteria.In a 4-y follow-up study that ended on 8 June 2006, we retrospectively analyzed the symptoms, underlying diseases, and mortality of 120 adult non-HIV patients with NTM culture findings obtained between 1990 and 1998. We categorized the patients according to the 2007 ATS NTM case definition into positive and negative groups.Only 61/120 patients (51%) fulfilled the ATS criteria for NTM disease. As compared to ATS-negative subjects, the ATS-positive group showed lower age, a higher proportion of females, and fewer fatal underlying diseases. Among ATS-negative subjects, 46/59 (78%) did not fulfil the microbiological criteria and 43/59 (73%) did not fulfil the radiological criteria. Mycobacterium avium complex (MAC) comprised 61% of isolations in the ATS-positive and 47% in the ATS-negative group (p = 0.15). No significant difference in median survival time was found between the groups: ATS-positive 7.4 y (95% confidence interval (CI) 0.2-14.6) and ATS-negative 5.3 y (95% CI 3.0-7.6). No significant difference was found in symptoms except fatigue, which was more common in the ATS-positive (56% vs 37%, p = 0.04). Symptoms lasted for less than a year in 48%, which suggests a more rapid disease progression than has previously been reported.The fulfillment of ATS criteria was poorly associated with any difference in prognosis, and based on our findings would be a poor prognostic marker.

An association exists between chronic infection-induced inflammation, such as periodontitis, and acute coronary syndrome (ACS). We studied the association of serum neutrophil markers, myeloperoxidase (MPO), matrix metalloproteinase (MMP)-8, tissue inhibitor of metalloproteinase (TIMP)-1 concentrations and MMP-8 ⁄TIMP-1 ratio, with the risk of recurrent ACS. Radiographic periodontal status was recorded from 141 patients with acute non-Q-wave infarction or unstable angina pectoris, who participated in a double-blind, placebo-controlled study with clarithromycin for 3 months. Serum samples were collected within arrival to the hospital, at 1 week, 3 months and 1 year. Recurrent ACS events were registered during the 1-year follow-up. In the whole population, high serum MPO concentrations at 1 week (fourth quartile versus quartiles 1‐3) were associated with the risk of recurrent ACS with a relative risk (RR) of 2.52 (95% CI, 1.277‐4.980; P = 0.008). In patients without periodontal disease, high MPO concentration at 1 week and 1 year predicted recurrent ACS with RRs of 3.54 (1.600‐7.831; P = 0.002) and 2.87 (1.171‐7.038; P = 0.021), respectively. In the placebo group, but not in the clarithromycin group, high serum MMP-8 ⁄TIMP-1 ratio at 1 week predicted recurrent ACS with an RR of 3.23 (1.295‐8.063; P = 0.012). Our results suggest that high serum neutrophil markers reflect increased risk of recurrent ACS, especially in patients without periodontal disease and not receiving antimicrobial medication.

We studied the possibility of detecting beta-hemolytic streptococcal infections by determining antibodies against the group specific polysaccharides from streptococci of groups A, A-variant, C and G. The methods used were radio-immunoassay with these four polysaccharides and hemagglutination of group A polysaccharide sensitized erythrocytes. Significant increases in these antibodies were rare in tonsillitis patients, whereas high concentrations of antibodies could often be observed in association with severe systemic infections or rheumatic fever. Both strictly immunogen-restricted and crossreactive antibodies could be demonstrated by isoelectric focusing and inhibition of antigen-binding. Although previously considered nonexistent, group specific carbohydrate antibodies of IgM class could also be demonstrated.

We found the prevalence of recurrent lymphocytic meningitis associated with herpes simplex virus type 2 (HSV-2) was 2.2/100,000 population in Finland during 1996–2006, higher than previous estimates. PCR was most sensitive in detecting HSV-2 DNA from cerebrospinal fluid if the sample was taken 2–5 days after symptom onset.

Two cases of penicillin-induced and one case of cephalosporin-induced leucopenia are described. This unusual complication of widely used beta-lactam antibiotics can occur when these antibiotics are administered parenterally in high doses for prolonged periods (14 days or more). The close monitoring of the white cell count is important when treating patients with high doses of beta-lactam antibiotics for prolonged periods. We would like to emphasize that when penicillin- or cephalosporin-induced leucopenia is suspected, continuation with another beta-lactam antibiotic may be dangerous.

The immune system may interplay between Chlamydia pneumoniae infection and coronary artery disease (CAD). Major histocompatibility complex genes regulate innate and adaptive immunity. Patients with CAD ( n = 100) and controls ( n = 74) were enrolled. Human leukocyte antigens (HLA-A, HLA-B, and HLA-DRB1), four lymphotoxin alpha single-nucleotide polymorphisms, and complement C4A and C4B allotypes were typed, and their haplotypes were inferred. The presence of serum C. pneumoniae immunoglobulin A (IgA) (titer, ≥40) or IgG (titer, ≥128) antibodies or immune complex (IC)-bound IgG antibodies (titer, ≥2) was considered to be a serological marker suggesting chronic C. pneumoniae infection. C. pneumoniae IgA antibodies were found more frequently in patients than in controls ( P = 0.04). Among the patients, multiple logistic regression analysis showed the HLA-B*35 allele to be the strongest-risk gene for C. pneumoniae infection (odds ratio, 7.88; 95% confidence interval, 2.44 to 25.43; P = 0.0006). Markers of C. pneumoniae infection were found more frequently in patients with the HLA-A*03-B*35 haplotype than in those without the haplotype ( P = 0.007 for IgA; P = 0.008 for IgG; P = 0.002 for IC). Smokers with HLA-B*35 or HLA-A*03-B*35 had markers of C. pneumoniae infection that appeared more often than in smokers without these genes ( P = 0.003 and P = 0.001, respectively). No associations were found in controls. In conclusion, HLA-B*35 may be the link between chronic C. pneumoniae infection and CAD.

Acute coronary syndrome is an inflammatory disease, during which the complement cascade is activated. We assessed the complement C3 and C4 concentration ratio (C3/C4 ratio) in serum as a potential measurement to predict cardiovascular attacks. Patients with acute coronary syndrome (n = 148) were followed after an initial attack for subsequent ischemic cardiovascular events (composite end point of death, myocardial infarction, recurrent unstable angina, or stroke). During the follow-up period (average 555 days), 44 patients met an end point. Blood samples were taken at hospitalization, 1 week, 3 months, and 1 year after hospital admission. Serum complement C3 and C4 concentrations and the C3/C4 ratio were analyzed. Patients with an end point had, throughout the follow-up period, a higher C3/C4 ratio than patients without these end points (repeated measures analysis of variance, p = 0.007). When all traditional cardiovascular risk factors and other potential confounding factors were included in a Cox multivariate logistic regression survival analysis, the C3/C4 ratio emerged as the novel risk factor for any new cardiovascular event (odds ratio 1.33, 95% confidence interval 1.08 to 1.63, p = 0.007). When the C3/C4 ratio was divided into 4 quartiles, 24% in quartiles 1 and 2 (lowest) and 48% in quartile 4 (highest) had end points during follow-up (odds ratio 3.04, 95% confidence interval 1.27 to 7.29, p = 0.01). In conclusion, increased serum C3/C4 ratio is a readily available and novel marker for recurrent cardiovascular events in acute coronary syndrome. The relative increase in serum C3 protein and decrease in C4 protein could explain changes in the C3/C4 ratio.

Inflammation leading to acute coronary syndrome may be triggered by bacteria causing periodontal infection. We investigated if recurrence of cardiovascular events in unstable coronary patients are associated with periodontitis or microbiological/serological markers of it. Periodontitis-related parameters of 141 patients with acute non-Q-wave infarction or unstable angina pectoris, who participated in a double-blind, placebo-controlled study with clarithromycin for 3 months, were adjusted to the occurrence of a recurrent cardiovascular event during a follow-up period (average 519 days). In the age group under 65 years the patients with periodontitis had a univariate odds ratios (OR) 95% confidence intervals (95% CI) of 5.0 (1.02-24.55) for a recurrent cardiovascular event in comparison with patients without periodontitis. Dental status correlated positively with serum lipopolysaccharide concentrations and combined IgG antibody response to Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. The end point frequency did not differ between clarithromycin and placebo groups in bacterium-positive, seropositive, or periodontitis patients. Fewer end points in clarithromycin group were seen in bacterium-negative, seronegative, edentulous, and non-periodontitis patients. Periodontitis and edentulousness are associated with recurrent cardiovascular events, especially in younger patients. Long-term clarithromycin therapy seems to be beneficial in prevention of recurrent cardiovascular events in non-periodontitis but not in periodontitis patients.

Background. Immunogenetic factors predisposing to recurrent genital herpes remain poorly characterized. Methods. In a prospective case-control study, 52 consecutive patients with frequently recurring outbreaks of genital herpes were compared with 80 herpes simplex virus (HSV)-seropositive (types 1 and 2) and 70 HSV-seronegative control subjects. Immunoglobulins (Igs), type-specific anti-HSV-2 IgG and IgG subclass antibodies against glycoprotein G, levels of C3 and C4, and classical pathway hemolytic complement activity were measured, and IgG1 and IgG3 allotyping; C4 immunophenotyping; C4* real-time polymerase chain reaction (PCR) genotyping; and HLA-A*, B*, and DR* typing were performed. Results. The G3m g ,G1m a/a(x) haplotype was more frequent in patients than in HSV-seronegative control subjects (P = .047). Compared with all control subjects, low levels of total IgG1 (odds ratio [OR], 4.9 [95% confidence interval {CI}, 2.0-12.5]; P = .001) and IgG3 (OR 3.6 [95% CI 1.7-7.8]; P = .001), but not of anti-HSV-2 antibodies, were associated with recurrences. Levels of complement were lowest in patients. The C4* null type was negatively associated with neuralgia (OR, 0.2 [95% CI, 0.06-0.81]; P = .022). Conclusions. Low levels of antibody-dependent cellular cytotoxicity-mediating IgGI and IgG3 antibodies, partly dependent of allotype, may predispose to recurrent genital herpes. Antibodies produced by T helper type 1 responses, potentially against an unknown epitope, appear to be relevant in recurrences. In patients, C4* deficiencies are associated with protection from herpetic neuralgias, possibly through reduced inflammation.

Background Data regarding antimicrobial susceptibility of clinical Lactobacillus isolates are scarce, and appropriate interpretation criteria for susceptibility tests are not available. Methods We examined 85 cases of Lactobacillus bacteremia, of which 47 cases have been included in our previous studies. Overall, 14 antimicrobial agents were evaluated by the E-test method, and these results were compared with disk diffusion test findings. The clinical outcomes of the patients and their antimicrobial treatments were registered. Results The antimicrobial susceptibility of Lactobacillus strains was species dependent. The considerable number of Lactobacillus rhamnosus (n=46), Lactobacillus fermentum (n=12), and Lactobacillus casei (n=12) strains available for testing made it possible to compare the susceptibilities within 1 species, as well. Of the 46 L. rhamnosus isolates, 22 were identified as L. rhamnosus GG type by pulsed-field gel electrophoresis. All Lactobacillus isolates demonstrated low minimum inhibitory concentrations (MICs) of imipenem, piperacillin-tazobactam, erythromycin, and clindamycin. MICs of vancomycin were high (>256 microg/mL) for all other species except Lactobacillus gasseri and Lactobacillus jensenii. Disk diffusion and E-test results were concordant. The MICs of cephalosporins varied; cefuroxime demonstrated a higher level of activity than did ceftriaxone. Benzylpenicillin and ampicillin MICs had variable ranges between different species. Combination therapy was given to 83% of the patients, but, in 54% of them, therapy included only 1 microbiologically active agent, according to results of the susceptibility tests. Mortality at 1 week was 12% among patients who presumably were receiving adequate treatment and 27% among patients who were receiving inadequate treatment (P=.131, by E-test). Conclusion Most clinical Lactobacillus blood isolates demonstrated low MICs of imipenem, piperacillin-tazobactam, erythromycin, and clindamycin, but they had variable susceptibility to penicillin and cephalosporins.

In Finland, Staphylococcus aureus bloodstream infections are caused predominantly (>99%) by methicillin-sensitive strains. In this study, laboratory-based surveillance data on Staphylococcus aureus bloodstream infections occurring in Finland from 1995 to 2001 were analyzed. Preceding hospitalizations for all persons with Staphylococcus aureus bloodstream infections were obtained from the national hospital discharge registry, and data on outcome was obtained from the national population registry. An infection was defined as nosocomial when a positive blood culture was obtained more than 2 days after hospital admission or within 2 days of admission if there was a preceding hospital discharge within 7 days. A total of 5,045 cases were identified. The annual incidence of Staphylococcus aureus bloodstream infection rose by 55%, from 11 per 100,000 population in 1995 to 17 in 2001. The increase was detected in all adult age groups, though it was most distinct in patients >74 years of age. Nosocomial infections accounted for 51% of cases, a proportion that remained unchanged. The 28-day death-to-case ratio ranged from 1% in the age group 1-14 years to 33% in patients >74 years of age. The 28-day death-to-case ratios for nosocomial and community-acquired infections were 22% and 13%, respectively, and did not change over time. The increase in incidence among elderly persons resulted in an increase in the annual rate of mortality associated with Staphylococcus aureus bloodstream infections, from 2.6 to 4.2 deaths per 100,000 population per year. Staphylococcus aureus bloodstream infections are increasing in Finland, a country with a very low prevalence of methicillin resistance. While the increase may be due in part to increased reporting, it also reflects a growing population at risk, affected by such factors as high age and/or severe comorbidity.

Although the 'test-and-treat' strategy is suggested as first-line therapy for uninvestigated dyspepsia, no large-scale studies in a real-life setting are available.1552 dyspeptic patients aged between 25 and 60 with no alarm symptoms were recruited to the study. After screening with a 13C-urea breath test, they were randomized into three treatment arms: Helicobacter pylori-positive either to eradication therapy with OAM (omeprazole, amoxycillin and metronidazole) (Hp+/erad) or omeprazole 20 mg daily (Hp+/ome) for 10 days, whereas H. pylori-negative patients (Hp-/ome) were treated with 20 mg omeprazole for 10 days. Gastrointestinal symptoms were registered at baseline at 1 and 2 years on the Gastrointestinal Symptom Rating Scale (GSRS) and quality of life with the Psychological General Well-Being index (PGWB). Additional visits, referrals for and number of endoscopies and their findings were registered during the 2 years' follow-up.Of the 1552 patients, 583 were H. pylori-positive (37.6%), and 288 of these were randomized for omeprazole and 295 to OAM. The Hp-/ome group had fewer general practitioner (GP) contacts (P0.0001) than the H. pylori-positive groups. Eradication therapy significantly improved general well-being and reduced upper gastrointestinal symptoms: abdominal pain (P=0.0001), heartburn (P=0.0061), acid regurgitation (P=0.003), hunger pain (P=0.009), especially in Hp+/erad. Peptic ulcer was found in 6.2%, 1.0%, 0.2% in Hp+/ome, Hp-+/erad and Hp-/ome, respectively (P=0.0007). Only 3 patients (1.0%) developed peptic ulcers in Hp-+/erad, all eradication failures.In uninvestigated dyspepsia, a negative test result for H. pylori reduces the number of GP contacts and endoscopy referrals compared to H. pylori-positive regardless of eradication therapy. Applied in real life, the test-and-treat strategy failed to reduce the number of endoscopies, but significantly reduced peptic ulcer disease and improved dyspeptic symptoms and quality of life.

The aim of the retrospective case-control study presented here was to elucidate the incidence, risk factors, and outcomes of nosocomial infections caused by quinolone-resistant Escherichia coli (QREC). During the 3-year period studied, 51 nosocomial QREC infections were found, and the characteristics of these cases were compared with those of 102 control patients with quinolone-susceptible nosocomial infections. In the multivariate analysis, risk factors were identified as prior quinolone therapy (odds ratio [OR], 18.49; 95% confidence interval [CI], 5.53-61.82; P value

The ability to adhere to human intestinal mucus was tested for lactic acid bacteria of clinical blood culture, human fecal and dairy origin. The blood culture isolates were found to adhere better than the dairy strains. Of the Lactobacillus rhamnosus strains (nine clinical, 10 fecal and three dairy), blood culture isolates adhered better than the fecal strains. Although these results indicate a trend for blood culture isolates to bind to intestinal mucus in higher numbers than strains of dairy and human fecal origin, other factors are also likely to be involved in the etiology of lactobacillemia since some of the clinical Lactobacillus isolates exhibited a relatively low level of adhesion.

The efficacy of antibiotic prophylaxis in cardiac surgery was compared between 97 patients receiving a single 2 g dosage of ceftriaxone and 103 receiving 500 mg of vancomycin i.v. every 6 h for 48 h. The overall infection rate was 13.4% in the ceftriaxone and 10.7% in the vancomycin group. Four (4%) wound infections, including one mediastinitis, occurred in the ceftriaxone group and five (5%) in the vancomycin group, with no statistically significant difference. The findings of this study support the adequacy of a simple single dose of ceftriaxone prophylaxis in cardiac surgery, at least in hospitals with low incidence of vancomycin-resistant staphylococcal infections.

All 134 episodes of bacteremia caused solely by Pseudomonas aeruginosa in a university hospital in the periods 1976-1982 and 1992-1996 were reviewed retrospectively to determine the clinical manifestations, outcome and prognostic factors. The mortality for the 30-day interval after drawing the first positive blood culture was 41%, but dropped from 53% in the first period to 29% in the second period (P=0.006). Mortality was highest in patients treated with an aminoglycoside only, as against those treated with other appropriate antibiotics (55% versus 25%, P=0.001). Over the two decades studied, use of an aminoglycoside only decreased, use of paracetamol (=acetaminophen) increased, and removal of both urinary and blood vessel catheters became more common. The mortality was 18% in patients with catheter removal (46% in the other patients, P=0.017) and 27% in patients who received paracetamol around the time of drawing the first positive blood culture (50% for the other patients, P=0.010). Logistic regression analysis showed that shock, central nervous system involvement, preceding thromboembolism and rapidly fatal underlying disease were associated with a fatal outcome, whereas catheter removal, appropriate antibiotic therapy and paracetamol therapy were associated with survival. The improved prognosis of Pseudomonas aeruginosa bacteremia over the two decades is thus due mainly to three changes in management of the infection: the more frequent use of new anti-pseudomonal beta-lactams and ciprofloxacin instead of aminoglycosides as monotherapy; the more frequent practice of removing catheters; and the increased use of paracetamol around the time of drawing the first positive blood sample.

The HLA-B27 tissue antigen is associated with reactive arthritis caused by different bacterial infections but its occurrence in purulent arthritis has not been studied earlier. We analysed the frequency of HLA-B27 in patients with culture proven purulent arthritis caused by Staphylococcus aureus or beta-haemolytic streptococci. The study included 41 patients treated during the years 1979-96 (15 female and 26 male) with a mean age of 52 years (range 16-80 years). HLA-B27 was found in 24% (9/37) of the tested patients compared with 14% in the healthy Finnish population, but the difference was not statistically significant (P0.50). No statistical difference in disease activity according to febrile days or duration of the disease could be found between HLA-B27 positive and negative patients. We conclude that HLA-B27 is not a risk factor for purulent arthritis, and when present it has no significant modifying effect on the clinical picture of purulent arthritis.

All cases of bacteremia caused solely by Escherichia coli in 1977-1979, 1987-1989, and 1993-1994 in a Finnish university hospital were reviewed retrospectively to determine the clinical manifestations, the outcome, and the prognostic factors. In 332 episodes, mortality during the month after the first positive blood culture was 17%. This figure diminished during the study period from 23% in the 1970s to 9% in the 1990s (p = 0.028). Mortality was lowest among patients treated with a combination of antibiotics, 7% versus 18% among those treated otherwise (p = 0.034). The use of acetaminophen increased during the study period from 18 to 55%. Mortality among patients who received acetaminophen within a period24 h to 48 h of the first positive blood culture was 10% versus 22% among others (p = 0.002). Logistic regression analysis showed six factors predictive of a fatal outcome: pneumonia, no known focus, shock, CNS disorder, thromboembolism, and rapidly fatal underlying disease. Appropriate antibiotic therapy predicted survival. In the analysis, replacement of appropriate antibiotic therapy by acetaminophen revealed that this drug was significantly associated with survival.

In order to analyse possible triggering or contributing infections and HLA-B27 frequency in patients with acute febrile joint syndrome fulfilling the proposed criteria of adult Still's disease (AOSD), we studied prospectively the serological findings of 25 patients. They were aged 15–62 years and diagnosed between 1978–1992, We then compared results with a control group consisting of 119 healthy persons. Positive viral or bacterial serology was found in 12 patients (48%) in the AOSD group compared with 13 cases (11%) in the control group (p< 0.001). Fourfold or higher viral antibody rise was found in two patients and bacterial antibody rise in three patients. High stable viral antibody titre was observed in one patient and high stable bacterial antibody titre in six patients. HLA-B27 was not overrepresented in the study group (12%) compared with a healthy Finnish population (14%). We conclude that many different bacterial and viral infections may trigger or contribute to AOSD.

The objective of this study was to characterize the overgrowth and susceptibility of Enterococcus faecium, compared with that of other enterococci, in the feces of patients with hematologic malignancy. During a 52-week period, surveillance samples of feces were cultured weekly. Three hundred thirty-three samples were obtained from 92 patients. E. faecium outnumbered other enterococci in 170 (44%) of the samples, while the opposite was true in 119 (31%) of the samples. Fecal overgrowth of E. faecium (> or = 9.0 log10 cfu/g) was found in 62 samples (16%), while overgrowth of other enterococci was documented in 20 samples (5%) (P < .001). Treatment with third-generation cephalosporins preceded the overgrowth of E. faecium in 93% of the patients. Resistance of E. faecium isolates to ampicillin, high-level gentamicin, and vancomycin was detected in 41%, 4%, and 2% of the patients, respectively. There were 6 patients with enterococcal bacteremia (due to E. faecium in 5 and Enterococcus faecalis in 1) during the study period. The high prevalence of resistance to ampicillin and imipenem rendered few (if any) intravenous antibiotics able to prevent fecal overgrowth of E. faecium.

The clinical significance of nontuberculous mycobacterial isolates and presentation of mycobacteriosis was compared in HIV-negative patients with or without preceding immunosuppression. Patients with nontuberculous mycobacterial isolates (n=139), mainly from the respiratory system, were divided into three groups: those who had had previous immunosuppressive treatment (24 %), those with other underlying diseases (54 %) and those without predisposing factors (22 %). The distribution of mycobacterial species among the various patient groups was similar. The immunosuppressed patients fulfilled the criteria of the American Thoracic Society for clinical mycobacteriosis less frequently (18 %) than those with other underlying diseases (32 %) or without predisposing factors (45 %), p=0.07, the difference being more striking for patients withMycobacterium avium complex isolates. This was partly due to the difficulty in distinguishing the relevant symptoms from those caused by the underlying disease. The proportion of patients receiving antimycobacterial therapy differed similarly (18 %, 21 %, 45 %, respectively). Among the immunosuppressed patients, positive acid-fast smears were significantly less common and polymicrobial infections, initial lymphocytopenia, fever and fatal outcome significantly more common. About half of the immunosuppressed patients died within one year. In order to better define patients requiring treatment, the criteria for localized mycobacteriosis among immunosuppressed patients should be reevaluated.

Several recent studies have suggested that dental infections are associated with coronary artery disease. To further elucidate this association, we conducted a prospective 7-year follow-up study of 214 individuals (182 males and 32 females; mean age, 49 years) with proven coronary artery disease who had undergone a dental examination and evaluation for the classic coronary risk factors at entry. The main outcome measures were the incidence of fatal and nonfatal coronary events and overall mortality. Fifty-two patients met the endpoint criteria during follow-up. Dental health was a significant predictor of coronary events when controlled for the following factors: age, sex, socioeconomic status, smoking, hypertension, the number of previous myocardial infarctions, diabetes, body mass index, and serum lipids. Other significant predictors were the presence of diabetes, the number of previous myocardial infarctions, and the body mass index. Our results give further support to the hypothesis that dental infections are a risk factor for coronary events.

An association exists between chronic infection-induced inflammation, such as periodontitis, and acute coronary syndrome (ACS). We studied the association of serum neutrophil markers, myeloperoxidase (MPO), matrix metalloproteinase (MMP)-8, tissue inhibitor of metalloproteinase (TIMP)-1 concentrations and MMP-8/TIMP-1 ratio, with the risk of recurrent ACS. Radiographic periodontal status was recorded from 141 patients with acute non-Q-wave infarction or unstable angina pectoris, who participated in a double-blind, placebo-controlled study with clarithromycin for 3 months. Serum samples were collected within arrival to the hospital, at 1 week, 3 months and 1 year. Recurrent ACS events were registered during the 1-year follow-up. In the whole population, high serum MPO concentrations at 1 week (fourth quartile versus quartiles 1-3) were associated with the risk of recurrent ACS with a relative risk (RR) of 2.52 (95% CI, 1.277-4.980; P = 0.008). In patients without periodontal disease, high MPO concentration at 1 week and 1 year predicted recurrent ACS with RRs of 3.54 (1.600-7.831; P = 0.002) and 2.87 (1.171-7.038; P = 0.021), respectively. In the placebo group, but not in the clarithromycin group, high serum MMP-8/TIMP-1 ratio at 1 week predicted recurrent ACS with an RR of 3.23 (1.295-8.063; P = 0.012). Our results suggest that high serum neutrophil markers reflect increased risk of recurrent ACS, especially in patients without periodontal disease and not receiving antimicrobial medication.

An association between dental and other bacterial infections and coronary heart disease has recently been observed in both cross-sectional and longitudinal studies. To elucidate this topic, the severity of dental infections and coronary atheromatosis was assessed, together with measurements of the conventional coronary risk factors, in 100 individuals (88 men, 12 women, mean age 48, range 28-68 years) referred for diagnostic coronary angiography. Pantomography X-rays and coronary angiograms of the participants were scored blindly by single observers, a dentist and a radiologist respectively. The median pantomography score was 3.0 in male individuals belonging to the highest tertile of coronary atheromatosis score, as compared with 0.0 among the rest of the male participants (P = 0.003). The association between dental infections and severe coronary atheromatosis in males remained significant after adjusting for the effect of age, blood lipids, body mass index, hypertension, smoking and social class. No association between dental infections and coronary atheromatosis was observed in the small number of females studied. This observation supports the proposal that bacterial infections play a role in the pathogenesis of coronary atherosclerosis.

OBJECTIVES--The purpose of this study was to analyse retrospectively adult patients with acute joint or muscle symptoms and a high antistreptolysin O (ASO) titre to find out which syndromes of clinical arthritis are associated with serological evidence of streptococcal infection. METHODS--Seventy six adult patients with an acute arthritis syndrome or an exacerbation in their chronic rheumatic disease and simultaneously a high ASO titre (> or = 500 Todd units) were examined in two time periods in the 1980s. RESULTS--Twenty six patients had arthritis associated with a known rheumatic disease, 25 had non-specific arthralgia/myalgia, 20 had reactive arthritis, and five had septic arthritis. No case of classic rheumatic fever classified by two major criteria was found. Six patients fulfilled one major and at least two minor criteria. The frequency of HLA-B27 was significantly higher in the whole patient group than in the healthy Finnish population (30 v 14%). CONCLUSIONS--It is concluded that classic rheumatic fever is now rare, even in patients with arthritis with a high ASO titre. These results support the suggestion that beta haemolytic streptococci may trigger reactive arthritis as well as rheumatic fever.

Non-tuberculous mycobacteria (NTM) cause infections in patients with smoking-related chronic lung diseases and also in non-smoking healthy elderly women. We analyzed the clinical symptoms, underlying diseases and mortality in patients with NTM culture findings, with special emphasis on smoking status.A total of 120 consecutive adult HIV-negative patients with NTM isolation were followed between 1990 and 1998 by retrieving data from their medical records for a period of at least 4 y, until 8 June 2006. Their clinical pictures and outcomes were analysed according to smoking status.In this study, 42% of the patients had never smoked. Females accounted for 72% of non-smokers, but only 30% of smokers (p0.001). Mycobacterium avium complex (MAC) accounted for 72% of all isolates in non-smokers and 41% in smokers (p = 0.001). Furthermore, 28% of non-smokers and 19% of smokers had no previous pulmonary diseases (p = 0.223). In nearly half of all patients (48%), symptoms of NTM infection started within a year prior to NTM isolation. Smokers had a higher risk of mortality compared to non-smokers (hazard ratio 1.64, p = 0.049), though this was not found after adjusting for underlying diseases. No fatal underlying diseases were found for 82% of non-smokers and 59% of smokers (p0.01).Non-smokers with NTM isolates had fewer previous lung diseases but had a higher incidence of MAC and bronchiectasis. Time from symptoms to NTM isolation was shorter than previously reported.

Unorganized care on chronic wounds is expensive. Resources are focused on the care of complicated wounds, although a significant proportion of the wounds could be prevented or treated at an early stage. Good care is cost-effective, a delayed care and inoperative treatment chain will waste money and resources. Specialization of medical and nursing staff in wound care will improve treatment outcome. Prerequisites for the necessary care must be guaranteed by creating a complete treatment path for problematic wounds in the capital region.

A growing amount of clinical and experimental evidence suggests a link between infection and atherosclerotic diseases including both myocardial and cerebral infarction. A prime example is a greatly increased risk of stroke in septicaemic patients with and without endocarditis. Controlled clinical studies have recently shown, however, that certain other milder bacterial infections are also a risk factor for infarction. A preceding febrile respiratory infection was a major risk factor for stroke in young and middle aged patients. In patients with acute myocardial infarction Chlamydia pneumoniae and dental infections seem to be risk factors according to one controlled clinical study. Several possible mechanisms could explain the observed association of infection and infarction. For instance, infection causes a hypercoagulable state which increases the risk of thrombosis. In addition, infection has profound and harmful effects on prostaglandin and lipid metabolism. Infection may also have some role in the atherosclerotic process itself by inducing damage and inflammation in vascular endothelium in the presence of hypercholesterolemia. So far, however, little clinical evidence is available to suggest that by controlling infection the risk of infarction or development of atherosclerotic lesions might be reduced except in patients with endocarditis, where the risk of thromboembolic complications rapidly diminished when the infection is controlled with antimicrobial therapy.

Fifty-eight adult patients treated with aortic valve replacement for infective endocarditis were retrospectively reviewed. The operation was performed during antibiotic therapy (group I, n = 25) or after completion of such therapy, on average 17 months after diagnosis (group II, n = 33). Preoperatively 68% of group I and 24% of group II were in NYHA class IV. Bacterial aetiology was verified in 78% of all cases. Preoperative embolic complications occurred in six group I and three group II cases, causing hemiplegia in eight. At operation the aortic valve was bicuspid in 29 of the 58 patients. Vegetations and cusp perforation were present in most cases. Bacteria were demonstrated in 11 of the excised specimens. A mechanical valve prosthesis was inserted in all cases. Three patients died, one perioperatively and two during their time in hospital (2 from group I). Low-output syndrome was the commonest postoperative complication. During follow-up averaging 66 months, 12 patients died (6 of cardiac causes). Late complications were periprosthetic leakage (2 cases), significant embolism (5), and prosthetic valve endocarditis (4), causing periprosthetic leakage in one case.

A growing amount of epidemiologic, experimental, and clinical evidence has linked infection as a risk factor to variousatherosclerotic diseases including acute myocardial infarction and cerebral infarction. Bacteremic infections with and without endocarditis carry a high risk for both stroke and acute myocardial infarction. During the last decade, chronic bacterial infections such as Chlamydia pneumoniae and dental infections have been associated as risk factors for various atherosclerotic diseases. These chronic bacterial infections are risk factors for acute cardiovascular events, but they may also have some role in the etiopathogenesis of atherosclerotic process itself. There are many known mechanisms that might explain the observed association of infection and atherosclerotic diseases, but it is probable that these mechanisms are complex and multifactorial and probably differ from infection to infection and from patient to patient. Infection theory is by no means against classic risk factor theory in the etiopathogenesis of atherosclerosis. Infection may also act as a synergistic risk factor together with classic risk factors in the development of various atherosclerotic diseases.

Periodontitis and coronary artery disease (CAD) are inflammatory diseases and associated with each other. The major histocompatibility complex (MHC) region carries genes involved in immune response and inflammation. We investigated whether the MHC genes correlate with the presence of periodontitis or with the occurrence of periodontal pathogens in patients with CAD. Blood and saliva samples from CAD patients (n = 106) were collected at the time of hospitalization. Nine MHC genetic markers [human leukocyte antigen (HLA)-A, HLA-B, HLA-DRB1, lymphotoxin alpha (LTA) +253(a/g), +496(C/T), +633(c/g), +724(C/A), C4A and C4B)] were typed. Based on panoramic tomography, patients were categorized into nonperiodontitis and periodontitis groups. Two major periodontal pathogens, Aggregatibacter (Actinobacillus) actinomycetemcomitans and Porphyromonas gingivalis, were cultivated and polymerase chain reaction-amplified from salivary samples. Serum immunoglobulin (Ig)A and IgG antibody levels to these pathogens were measured. In the univariate analysis, LTA+496C allele (OR = 5.29; 95% CI = 2.07-13.51, P = 0.00027), and the occurrence of P. gingivalis in saliva (OR = 4.74; 95% CI = 1.64-13.70; P = 0.002) were more frequent in periodontitis when compared with nonperiodontitis. Similarly, serum IgA antibody level against the pathogen was increased in periodontitis (P = 0.048). In the multiple logistic regression analysis, when a wide range of covariates was included, the LTA+496C allele (OR = 10.87; 95% CI = 3.23-36.60; P = 0.00012) and the elevated serum IgA antibody level against P. gingivalis (OR = 1.56; 95% CI = 1.05-2.30; P = 0.026) remained as significant risk factors for periodontitis. In conclusion, the major finding of this study is that the LTA+496C allele is associated with periodontitis in patients with CAD.

On 18 October 2007, the first case of Clostridium difficile PCR ribotype 027-associated disease was detected in Finland.

Despite rather strict recommendations for antibiotic treatment of disseminated Lyme borreliosis (LB), evidence-based studies on the duration of antibiotic treatment are scarce. The aim of this multicenter study was to determine whether initial treatment with intravenous ceftriaxone (CRO) for 3 weeks should be extended with a period of adjunct oral antibiotic therapy. A total of 152 consecutive patients with LB were randomized in a double-blind fashion to receive either amoxicillin (AMOX) 1 g or placebo (PBO) twice daily for 100 days. Both groups received an initial treatment of intravenous CRO 2 g daily for 3 weeks, followed by the randomized drug or PBO. The outcome was evaluated using the visual analogue scale at the follow-up visits. The final analysis included 145 patients, of whom 73 received AMOX and 72 PBO. Diagnoses of LB were categorized as either definite or possible, on the basis of symptoms, signs, and laboratory results. The diagnosis was definite in 52 of the 73 (71.2%) AMOX-treated patients and in 54 of the 72 (75%) PBO patients. Of the patients with definite diagnoses, 62 had neuroborreliosis, 45 arthritis or other musculoskeletal manifestations, and 4 other manifestations of LB. As judged by the visual analogue scale and patient records, the outcome after a 1-year follow-up period was excellent or good in 114 (78.6%) patients, controversial in 14 (9.7%) patients, and poor in 17 (11.7%) patients. In patients with definite LB, the outcome was excellent or good in 49 (92.5%) AMOX-treated patients and 47 (87.0%) PBO patients and poor in 3 (5.7%) AMOX-treated patients and 6 (11.1%) PBO patients (difference nonsignificant, p = 0.49). Twelve months after the end of intravenous antibiotic therapy, the levels of antibodies against Borrelia burgdorferi were markedly decreased in 50% of the patients with definite LB in both groups. The results indicate that oral adjunct antibiotics are not justified in the treatment of patients with disseminated LB who initially receive intravenous CRO for 3 weeks. The clinical outcome cannot be evaluated at the completion of intravenous antibiotic treatment but rather 6–12 months afterwards. In patients with chronic post-treatment symptoms, persistent positive levels of antibodies do not seem to provide any useful information for further care of the patient.

Severe forms of chronic periodontitis affect up to 10% of adults. Tumour necrosis factor and lymphotoxin-alpha genes in the major histocompatibility complex are associated with severe periodontitis. Complement factor C4 is a nearby, polymorphic, functionally relevant gene region. Although associated with chronic mucosal infections, C4 deficiencies have not been assessed in adult periodontitis patients. We tested whether complement levels are systemically altered and C4 deficiencies associated with severe chronic periodontitis. In a case-control study, we analysed levels of plasma C3, and C4, serum classical pathway haemolytic activity, C4 allotypes and C4 gene numbers in 37 patients with severe chronic periodontitis and in 150 voluntary controls. Plasma levels of C3 were higher, and classical pathway haemolytic activity was lower in patients than in controls. Partial C4 gene deficiencies were more frequent in patients than in controls (odds ratio 2.4, 95% confidence interval 1.1-5.5, P = 0.032). Changes in complement levels may reflect chronic, recurring inflammation. C4 gene deficiencies are associated with predisposition to chronic periodontitis.

Aiming to study the role of human major histocompatibility complex (MHC) region on coronary artery disease (CAD), we enrolled two separate patient materials and controls. First, heart transplantation recipients (n = 276) were divided into three subgroups according to the severity of atherosclerosis. The human leukocyte antigen (HLA)-A-B-DR haplotype and gene frequencies were compared between groups. Second, patients with acute coronary syndrome (ACS) (n = 100) and healthy controls (n = 74) were assessed by nine genetic MHC markers (HLA-A, HLA-B, HLA-DRB1, LTA+253(a/g), LTA+496(C/T), LTA+633(c/g), LTA+724(C/A), C4A and C4B), and the frequencies were compared. In the heart transplantation recipients, HLA-DR1 was strongly associated with CAD [severe vs no evidence, odds ratio (OR) 2.37; 95% confidence interval (CI) 1.33-4.25; P = 0.003]. Similarly, in the patients with ACS, HLA-DRB1*01 was associated with CAD (patients vs controls, OR 2.36; 95% CI 1.25-4.44; P = 0.007). HLA-DRB1*01 was associated with low-density-lipoprotein cholesterol (OR 5.32; 95% CI 1.64-17.26; P = 0.005) and smoking habit (OR 3.13; 95% CI 1.09-9.03; P = 0.035) as risk factors. The strongest protective gene was HLA-B*07 alone (OR 0.46; 95% CI 0.24-0.88; P = 0.02) or together with the haplotype LTA+253a-LTA+633g-C4A3-C4B1 (OR 0.36; 95% CI 0.22-0.57; P = 0.00001). In conclusion, human MHC region harbors genes that protect from and predispose to CAD.