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Biomedical subjects

M Vaara

Publications and source records attributed to M Vaara.

At least 19 recordsLinked to original sources
PubMed2006

Levofloxacin does not decrease mortality in Staphylococcus aureus bacteraemia when added to the standard treatment: a prospective and randomized clinical trial of 381 patients.

OBJECTIVES: To study whether levofloxacin, added to standard treatment, could reduce the high mortality and complication rates in Staphylococcus aureus bacteraemia. DESIGN: A prospective randomized multicentre trial from January 2000 to August 2002. SETTING: Thirteen tertiary care or university hospitals in Finland. SUBJECTS: Three hundred and eighty-one adult patients with S. aureus bacteraemia. Patients with meningitis, and those with fluoroquinolone- or methicillin-resistant S. aureus were excluded. INTERVENTIONS: Standard treatment (mostly semisynthetic penicillin) (n = 190) or that combined with levofloxacin (n = 191). Supplementary rifampicin was recommended if deep infection was suspected. MAIN OUTCOME MEASURES: Primary end-points were mortality at 28 days and at 3 months. Clinical and laboratory parameters were analysed as secondary end-points. RESULTS: Adding levofloxacin to the standard treatment offered no survival benefit. Case fatality rates were 14% in both groups at 28 days, and 21% in the standard treatment and 18% in the levofloxacin group at 3 months. Levofloxacin combination did not differ from the standard treatment in the number of complications, time to defervescence, decrease in serum C-reactive protein concentration or length of antibiotic treatment. Deep infection was found in 84% of patients within 1 week following randomization with no difference between the treatment groups. At 3 months, the case fatality rate for patients with deep infection was 17% amongst those who received rifampicin versus 38% for those without rifampicin (P < 0.001, odds ratio = 3.06, 95% confidence intervals = 1.69-5.54). CONCLUSIONS: Levofloxacin combined with standard treatment in S. aureus bacteraemia did not decrease mortality or the incidence of deep infections, nor did it speed up recovery. Interestingly, deep infections in S. aureus bacteraemia appeared to be more common than previously reported.

Adult↗
PubMed2006

Postural balance in a random sample of 7,979 subjects aged 30 years and over.

BACKGROUND: Reliable normative data for force platform measurements of postural balance have not been available. METHODS: Data on postural balance were collected from a representative nationwide sample of a Finnish population aged >or=30 years (n = 7,979). As part of a comprehensive health survey (Health 2000), postural balance was measured with the help of a force platform system in four test conditions: normal standing with eyes open and closed (both for 30 s), semi-tandem (20 s) and tandem stand with eyes open (20 s). In addition, balance abilities were also evaluated by a non-instrumented field test. RESULTS: The main findings of this study indicated that the differences in balance between subjects belonging to different age categories were apparent already among young and middle-aged subjects. This is true, however, only for the more accurate force platform measurements, as the field test showed a clear ceiling effect up to 60 years of age. At higher ages both methods indicated a further, accelerating decline in balance function. In most cases, males tended to have more pronounced sway, as indicated by the speed and amplitude aspects of the movement of the center of pressure during the force platform registrations and these differences were larger in the older age groups. In contrast, in the field test a larger proportion of males were able to achieve the highest category (10 s in tandem stand) and the proportion of subjects unable to stand for a minimum of 10 s feet side by side was larger among females than males. These observations may partly be due to differences in the participation/acceptable performance in the different tests. In addition, the field test and force platform measurements may partially reflect different aspects of balance abilities. CONCLUSION: The results of the present study provide normative values for force platform balance tests at an age of 30 years and above. Deterioration in balance function clearly starts at relatively young ages and further accelerates from at about 60 years upwards. Due to systematic differences between males and females, separate normative values for both sexes are needed. Due to marked ceiling effects the field test can only be recommended for older individuals, aged >/=60. On the other hand, force platform registrations in the more demanding tests (semi-tandem and tandem stands) suffer from floor effects in the oldest age groups.

Adult↗
PubMed2004

Effects of a 6-month exercise program on patients with multiple sclerosis: a randomized study.

OBJECTIVE: To improve walking and other aspects of physical function with a progressive 6-month exercise program in patients with multiple sclerosis (MS). METHODS: MS patients with mild to moderate disability (Expanded Disability Status Scale scores 1.0 to 5.5) were randomly assigned to an exercise or control group. The intervention consisted of strength and aerobic training initiated during 3-week inpatient rehabilitation and continued for 23 weeks at home. The groups were evaluated at baseline and at 6 months. The primary outcome was walking speed, measured by 7.62 m and 500 m walk tests. Secondary outcomes included lower extremity strength, upper extremity endurance and dexterity, peak oxygen uptake, and static balance. An intention-to-treat analysis was used. RESULTS: Ninety-one (96%) of the 95 patients entering the study completed it. Change between groups was significant in the 7.62 m (p = 0.04) and 500 m walk tests (p = 0.01). In the 7.62 m walk test, 22% of the exercising patients showed clinically meaningful improvements. The exercise group also showed increased upper extremity endurance as compared to controls. No other noteworthy exercise-induced changes were observed. Exercise adherence varied considerably among the exercisers. CONCLUSIONS: Walking speed improved in this randomized study. The results confirm that exercise is safe for multiple sclerosis patients and should be recommended for those with mild to moderate disability.

Adult↗
PubMed2003

Safety of probiotics that contain lactobacilli or bifidobacteria.

Lactobacilli and bifidobacteria are extremely rare causes of infection in humans, as are probiotics based on these organisms. This lack of pathogenicity extends across all age groups and to immunocompromised individuals. Strains used for new probiotics should be chosen from the commensal flora of humans and should not carry intrinsic resistance to antibiotics that would prevent treatment of a rare probiotic infection. Vigilance regarding the detection of possible rare cases of infection due to probiotics should be maintained, and isolates should be sent to reference centers for molecular characterization and confirmation.

Bifidobacteriales Infections↗
PubMed2001

BRCT domain-containing protein TopBP1 functions in DNA replication and damage response.

Topoisomerase IIbeta-binding protein (TopBP1), a human protein with eight BRCT domains, is similar to Saccharomyces cerevisiae Dpb11 and Schizosaccharomyces pombe Cut5 checkpoint proteins and closely related to Drosophila Mus101. We show that human TopBP1 is required for DNA replication and that it interacts with DNA polymerase epsilon. In S phase TopBP1 colocalizes with Brca1 to foci that do not represent sites of ongoing DNA replication. Inhibition of DNA synthesis leads to relocalization of TopBP1 together with Brca1 to replication forks, suggesting a role in rescue of stalled forks. DNA damage induces formation of distinct TopBP1 foci that colocalize with Brca1 in S phase, but not in G(1) phase. We also show that TopBP1 interacts with the checkpoint protein hRad9. Thus, these results implicate TopBP1 in replication and checkpoint functions.

Animals↗
PubMed2001

Distribution of streptococcal inhibitor of complement variants in pharyngitis and invasive isolates in an epidemic of serotype M1 group A Streptococcus infection.

Streptococcal inhibitor of complement (Sic) is a highly polymorphic extracellular protein made predominantly by serotype M1 group A Streptococcus (GAS). New variants of the Sic protein frequently appear in M1 epidemics as a result of positive natural selection. To gain further understanding of the molecular basis of M1 epidemics, the sic gene was sequenced from 471 pharyngitis and 127 pyogenic and blood isolates recovered from 598 patients living in metropolitan Helsinki, Finland, during a 37-month population-based surveillance study. Most M1 GAS subclones recovered from pyogenic infections and blood were abundantly represented in the pool of subclones causing pharyngitis. Alleles shared among the pharyngitis, pyogenic, and blood samples were identified in throat isolates a mean of 9.8 months before their recovery from pyogenic infections and blood, which indicates that selection of most sic variants occurs on mucosal surfaces. In contrast, no variation was identified in the emm and covR/covS genes.

Alleles↗
PubMed2001

Clinical "pneumococcal pneumonia" due to Moraxella osloensis: case report and a review.

A previously healthy 6-y-old girl presented with a disease very similar to pneumococcal pneumonia. However, Moraxella osloensis was isolated by lung tap. The patient responded well to a course of parenteral penicillin. This is probably the first documented case of community-acquired pneumonia associated with this agent. Clinical isolates of M. osloensis are rare and its pathogenesis has not been delineated; however, a literature review suggests that the organism is more common than is generally recognized.

Child↗
PubMed2000

Intramucosal pH and endotoxin and cytokine release in severe acute pancreatitis.

It has been postulated that in severely ill patients splanchnic hypoperfusion may cause endotoxin release from the gut, and this leakage of endotoxin into the circulation can trigger the cascade of inflammatory cytokines. We tested this hypothesis in 9 patients with acute severe pancreatitis by monitoring gastric intramucosal pH (pHi) as measure of splanchnic hypoperfusion at 12-h intervals trying to correlate it to endotoxin and cytokine release. Only 3 of 59 samples, obtained from 3 patients contained circulating endotoxin. Thirteen of 15 plasma samples drawn at pHi <7.20 did not contain endotoxin. The pHi was significantly lower in patients who subsequently developed 3 or more organ failures (P = 0.0017, analysis of variance). Although endotoxemia was only occasionally found, most patients had measurable interleukin 1beta (IL-1beta), interleukin 6 (IL-6), interleukin 8 (IL-8), and interleukin 10 (IL-10) in their plasma. Concentrations of IL-6, IL-8, and IL-10 on admission correlated to degree of organ dysfunction as measured by the multiple organ system failure score (P = 0.035, r = 0.74; P = 0.010, r = 0.91; P = 0.021, r = 0.82, respectively). In conclusion, patients with acute, severe pancreatitis often have splanchnic hypoperfusion and produce a wide array of cytokines despite a rare occurrence of endotoxemia.

APACHE↗
PubMed1999

Interleukin 1 receptor antagonist and E-selectin concentrations: a comparison in patients with severe acute pancreatitis and severe sepsis.

PURPOSE: This prospective clinical study was designed to compare interleukin 1 receptor antagonist (IL-1ra) and E-selectin concentrations in patients with severe acute pancreatitis to those with severe sepsis. MATERIALS AND METHODS: Nine consecutive patients with severe acute pancreatitis and 11 consecutive patients with severe sepsis admitted to a medical/surgical intensive care unit were included in the study. Plasma concentrations of IL-1ra and E-selectin were serially measured daily for 7 days or throughout their stay in the intensive care unit if shorter. RESULTS: The concentrations of IL-1ra were significantly higher on admission in patients with severe sepsis compared with the patients with severe pancreatitis (median levels 10,500 and 2,600 pg/mL, respectively, P = .007). When the data from the first 3 days were analyzed using analysis of variance (ANOVA), the levels of IL-1ra and E-selectin were similar in both groups. The concentrations of IL-1ra and E-selectin correlated to the development of multiorgan dysfunction as assessed by sequential organ failure assessment (SOFA) score (P = .032 and .043, respectively). CONCLUSION: This study shows that IL-1ra and E-selectin are released in acute severe pancreatitis, and the levels seem to be comparable to those in patients with severe sepsis. Concentrations of IL-1ra and E-selectin correlate to the development of multiorgan failure as indicated by high SOFA scores during the first week of disease.

APACHE↗
PubMed1999

Outer membrane permeability barrier in Escherichia coli mutants that are defective in the late acyltransferases of lipid A biosynthesis.

The tight packing of six fatty acids in the lipid A constituent of lipopolysaccharide (LPS) has been proposed to contribute to the unusually low permeability of the outer membrane of gram-negative enteric bacteria to hydrophobic antibiotics. Here it is shown that the Escherichia coli msbB mutant, which elaborates defective, penta-acylated lipid A, is practically as resistant to a representative set of hydrophobic solutes (rifampin, fusidic acid, erythromycin, clindamycin, and azithromycin) as the parent-type control strain. The susceptibility index, i.e., the approximate ratio between the MIC for the msbB mutant and that for the parent-type control, was maximally 2.7-fold. In comparison, the rfa mutant defective in the deep core oligosaccharide part of LPS displayed indices ranging from 20 to 64. The lpxA and lpxD lipid A mutants had indices higher than 512. Furthermore, the msbB mutant was resistant to glycopeptides (vancomycin, teicoplanin), whereas the rfa, lpxA, and lpxD mutants were susceptible. The msbB htrB double mutant, which elaborates even-more-defective, partially tetra-acylated lipid A, was still less susceptible than the rfa mutant. These findings indicate that hexa-acylated lipid A is not a prerequisite for the normal function of the outer membrane permeability barrier.

Acyltransferases↗
PubMed1999

vanA and vanB incorporate into an endemic ampicillin-resistant vancomycin-sensitive Enterococcus faecium strain: effect on interpretation of clonality.

Clonal spread and horizontal transfer in the spread of vancomycin resistance genes were investigated. Multiplex PCR, pulsed-field gel electrophoresis (PFGE), hybridization of enterococcal plasmids with the vanA and vanB probes, and sequencing of a fragment of vanB were used in the analysis. Before May 1996, 12 vancomycin-resistant Enterococcus faecium (VRE) isolates were found in Finland. Between May 1996 and October 1997, 156 VRE isolates were found in the Helsinki area. Between December 1997 and April 1998, fecal samples from 359 patients were cultured for VRE. One new case of colonization with VRE was found. During the outbreak period, 88% (137 of 155) of the VRE isolates belonged to two strains (VRE types I and II), as determined by PFGE. Each VRE type I isolate possessed vanB, and five isolates also had vanA. Of the 34 VRE type II isolates, 27 possessed vanA and 7 possessed vanB. Fifteen of 21 (71%) ampicillin-resistant, vancomycin-sensitive E. faecium (VSE) isolates found during and after the outbreak period in one ward were also of type II. Two VSE type II isolates were found in the hospital before the outbreak in 1995. By PFGE, the three groups (vanA, vanB, or no van gene) of type II shared the same band differences with the main type of VRE type II with vanA. None of the differences was specific to or determinative for any of the groups. Our material suggests that vanA and vanB incorporate into an endemic ampicillin-resistant VSE strain.

Ampicillin Resistance↗
PubMed1998

Comparison of risk factors and outcome in patients with Enterococcus faecalis vs Enterococcus faecium bacteraemia.

The purpose of our study was to determine retrospectively the risk factors for the acquisition of Enterococcus faecalis vs E. faecium bacteraemia, as well as the clinical outcomes of these patients. 62 patients with Enterococcus faecalis bacteraemia were compared to 31 patients with E. faecium bacteraemia. Haematologic malignancies, neutropenia, high-risk source and previous use of aminoglycosides, carbapenems, cephalosporins and clindamycin were significantly associated with E. faecium bacteraemia. Instead, urinary catheterization was found to be related to Enterococcus faecalis bacteraemia. The mortality rates within 7 d and 30 d were 13% and 27%, respectively, in patients with E. faecalis bacteraemia and 6% and 29%, respectively, in patients with E. faecium bacteraemia. There was no difference in mortality between E. faecalis and E. faecium bacteraemia, nor was there a difference in seriousness of disease at the time of bacteraemia. In the subgroups of patients with monomicrobial or clinically significant E. faecalis vs E. faecium bacteraemia, the mortality rates were similar to the results of all subjects. Our results do not support the theory that E. faecium would be a more virulent organism than E. faecalis.

Adult↗
PubMed1997

Phosphate groups in lipopolysaccharides of Salmonella typhimurium rfaP mutants.

Lipopolysaccharides (LPS) of Salmonella typhimurium rfaP mutants and of a galE strain as a control were subjected to analysis by 31P-NMR in order to assess the location of phosphate groups. This was done to obtain direct proof for our earlier finding by chemical analysis that phosphate was lacking in the core oligosaccharide part of the mutant LPS, whereas the core oligosaccharide normally contains several phosphate groups. Such phosphate deficiency has been associated with the increased susceptibility of the rfaP mutants to hydrophobic antibiotics and detergents. Analysis of the de-O-acylated LPS derivatives of S. typhimurium rfaP strains SH7770, SH8551, and SH8572 by 31P-NMR revealed an almost total lack of phosphate groups in the core oligosaccharide part, the LPS phosphates being largely accounted for by the two monophosphate monoesters of lipid A, linked to positions C-1 and C-4' of the lipid A backbone. Core oligosaccharide-linked phosphates were detected in minor proportions only, indicating the presence of some normally phosphorylated core oligosaccharide, due to the inherently leaky nature of the mutation.

Carbohydrate Sequence↗
PubMed1997

Plasma interleukin-8, interleukin-10, and E-selectin levels in neutropenic and non-neutropenic bacteremic patients.

Plasma interleukin-8 (IL-8) interleukin-10 (IL-10), and E-selectin concentrations were studied in 39 neutropenic and 30 non-neutropenic bacteremic patients; 54 nonbacteremic patients were analyzed as controls. Interleukin-8 concentrations were significantly higher in neutropenic than in non-neutropenic bacteremic patients (median 475 vs. 0 pg/ml, p < 0.0001). Median IL-8 and IL-10 levels were higher in bacteremic than in non-bacteremic patients (330 vs. 0 pg/ml, p < 0.0001 and 20 vs. 0 pg/ml, p = 0.04, respectively). In contrast, concentrations of IL-10 were similar in neutropenic and non-neutropenic patients. Median levels of E-selectin were not increased in any of the patient groups. Neutropenic bacteremic patients showed significantly lower concentrations of E-selectin than did non-neutropenic bacteremic patients (p < 0.0001). In conclusion, neutropenic bacteremic patients had significantly higher concentrations of IL-8 than non-neutropenic bacteremic patients. Levels of IL-10 were higher in bacteremic than in nonbacteremic patients, but neutropenic and non-neutropenic patients had similar levels of IL-10. Increased levels of E-selectin were not found in any of the patient groups, although neutropenic patients with bacteremia had lower concentrations than did non-neutropenic patients.

Adult↗