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1.
Acta Anaesthesiol Scand ; 61(1): 53-61, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27514616

ABSTRACT

BACKGROUND: Knowledge of sepsis-related end-organ inflammation in vivo is limited. We investigated the cytokine response in skin and in serum in sepsis and its relation to multiorgan failure (MOF) and survival. METHODS: Cytokines were analysed in serum and in suction blister fluid of intact skin of 44 patients with severe sepsis and 15 healthy controls. Blister fluid and serum samples were collected within 48 h of the first sepsis-induced organ failure. This is a substudy of a larger follow-up study on wound healing in sepsis. RESULTS: Cytokine levels were higher in patients with sepsis vs. controls (interleukin [IL]-10, blisters: 65.9 vs. 4.3 pg/ml, P < 0.001, serum: 25.7 vs. 4.5 pg/ml, P = 0.004; IL-6, blisters: 41.9 vs. 0.03 pg/ml, P < 0.001, serum: 45.5 vs. 2.1 pg/ml, P < 0.001). Patients with MOF had higher levels of IL-10 (116.4 vs. 21.3 pg/ml, P = 0.015), IL-4 (0.7 vs. 0.07 pg/ml, P = 0.013) and basic fibroblast growth factor (bFGF) (25.9 vs. 9.5 pg/ml, P = 0.027) in blister fluid than patients without MOF. In blister fluid, survivors had lower levels of IL-10 (43.3 vs. 181.9 pg/ml, P = 0.024) and bFGF (15.8 vs. 31.9 pg/ml, P = 0.006) than non-survivors. In serum, survivors had higher levels of vascular endothelial growth factor (VEGF) (152.2 vs. 14.7 pg/ml, P = 0.012) and lower levels of IL-6 (38.5 vs. 91.1 pg/ml, P = 0.011) than non-survivors. The blister fluid levels of bFGF, TNF and VEGF did not correlate with the serum levels. CONCLUSIONS: Cytokine responses in skin blister fluid in patients with sepsis differed from those in healthy controls.


Subject(s)
Blister/immunology , Cytokines/analysis , Sepsis/immunology , Skin/immunology , Wound Healing/physiology , Aged , Humans , Hydrocortisone/therapeutic use , Middle Aged , Multiple Organ Failure/immunology , Sepsis/drug therapy , Sepsis/mortality
2.
Vet Comp Oncol ; 14(4): 395-408, 2016 Dec.
Article in English | MEDLINE | ID: mdl-25302859

ABSTRACT

Cancer is one of the most common reasons for death in dogs. One promising approach is oncolytic virotherapy. We assessed the oncolytic effect of genetically modified vaccinia viruses in canine cancer cells, in freshly excised tumour biopsies, and in mice harbouring canine tumour xenografts. Tumour transduction efficacy was assessed using virus expressing luciferase or fluorescent marker genes and oncolysis was quantified by a colorimetric cell viability assay. Oncolytic efficacy in vivo was evaluated in a nude mouse xenograft model. Vaccinia virus was shown to infect most tested canine cancer cell lines and primary surgical tumour tissues. Virus infection significantly reduced tumour growth in the xenograft model. Oncolytic vaccinia virus has antitumour effects against canine cancer cells and experimental tumours and is able to replicate in freshly excised patient tumour tissue. Our results suggest that oncolytic vaccinia virus may offer an effective treatment option for otherwise incurable canine tumours.


Subject(s)
Dog Diseases/therapy , Neoplasms/veterinary , Oncolytic Virotherapy , Vaccinia virus/physiology , Animals , Biopsy , Cell Line, Tumor , Dog Diseases/pathology , Dogs , Mice, Nude , Neoplasms/pathology , Neoplasms/virology , Neoplasms, Experimental/therapy , Oncolytic Viruses
3.
Acta Anaesthesiol Scand ; 59(8): 1009-14, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26032240

ABSTRACT

BACKGROUND: An intact basement membrane at the dermal-epidermal junction is essential to the viability of the skin. The effect of sepsis on the basement membrane is unknown. METHODS: Skin biopsies were used to study basement membrane structure in severe sepsis (Day 1). Subsequent biopsies were taken on Day 8 and at 3 months in the survivors. Immunohistochemical staining was undertaken using laminin-223 and type IV collagen. Twenty patients with severe sepsis and four control subjects were included in the analysis. RESULTS: Intensive care unit mortality was 4/20, and total 30-day mortality was 5/20. Exactly, 7/17 of patients with severe sepsis exhibited weak or absent laminin-332 expression and 11/15 exhibited weak or absent type IV collagen expression compared with 0/4 of control subjects on Day 1 in intact skin. The proportion of sepsis patients with weak or absent laminin-332 expression was 5/11 on Day 8 and fell to 1/7 at 3 months. The proportion of sepsis patients with weak or absent type IV collagen expression was 10/11 on Day 8 and 4/7 at 3 months. CONCLUSION: These findings suggest that basement membrane formation may be compromised in patients with severe sepsis.


Subject(s)
Collagen Type IV/metabolism , Laminin/metabolism , Sepsis/metabolism , Skin/metabolism , Adult , Aged , Aged, 80 and over , Basement Membrane/metabolism , Female , Follow-Up Studies , Humans , Immunohistochemistry , Male , Middle Aged
4.
Gene Ther ; 22(1): 65-75, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25231172

ABSTRACT

In our earlier studies, Semliki Forest virus vector VA7 completely eliminated type I interferon (IFN-I)-unresponsive human U87-luc glioma xenografts, whereas interferon-responsive mouse gliomas proved refractory. Here, we describe in two clones of CT26 murine colon carcinoma, opposed patterns of IFN-I responsiveness and sensitivity to VA7. Both CT26WT and CT26LacZ clones secreted biologically active interferon in vitro upon virus infection but only CT26WT cells were protected. Focal infection of CT26WT cultures was self-limiting but could be rescued using IFN-I pathway inhibitor Ruxolitinib or antibody against IFNß. Whole transcriptome sequencing (RNA-Seq) and protein expression analysis revealed that CT26WT cells constitutively expressed 56 different genes associated with pattern recognition and IFN-I signaling pathways, spanning two reported anti-RNA virus gene signatures and 22 genes with reported anti-alphaviral activity. Whereas CT26WT tumors were strictly virus-resistant in vivo, infection of CT26LacZ tumors resulted in complete tumor eradication in both immunocompetent and severe combined immune deficient mice. In double-flank transplantation experiments, CT26WT tumors grew despite successful eradication of CT26LacZ tumors from the contralateral flank. Tumor growth progressed uninhibited also when CT26LacZ inoculums contained only a small fraction of CT26WT cells, demonstrating dominance of IFN responsiveness when heterogeneous tumors are targeted with interferon-sensitive oncolytic viruses.


Subject(s)
Colonic Neoplasms/therapy , Oncolytic Virotherapy , Oncolytic Viruses/genetics , Semliki forest virus/genetics , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Bystander Effect , Cell Line, Tumor , Colonic Neoplasms/immunology , Colonic Neoplasms/pathology , Genetic Vectors , Green Fluorescent Proteins/biosynthesis , Interferon Type I/pharmacology , Interferon Type I/therapeutic use , Interferon-beta/metabolism , Mice, Inbred BALB C , Necrosis , Neoplasm Transplantation , STAT1 Transcription Factor/metabolism , Transfection , Treatment Outcome
5.
Int J Cancer ; 134(12): 2878-90, 2014 Jun 15.
Article in English | MEDLINE | ID: mdl-24248808

ABSTRACT

At present, it is not possible to reliably identify patients who will benefit from oncolytic virus treatments. Conventional modalities such as computed tomography (CT), which measure tumor size, are unreliable owing to inflammation-induced tumor swelling. We hypothesized that magnetic resonance imaging (MRI) and spectroscopy (MRS) might be useful in this regard. However, little previous data exist and neither oncolytic adenovirus nor immunocompetent models have been assessed by MRS. Here, we provide evidence that in T2-weighted MRI a hypointense core area, consistent with coagulative necrosis, develops in immunocompetent Syrian hamster carcinomas that respond to oncolytic adenovirus treatment. The same phenomenon was observed in a neuroblastoma patient while he responded to the treatment. With relapse at a later stage, however, the tumor of this patient became moderately hyperintense. We found that MRS of taurine, choline and unsaturated fatty acids can be useful early indicators of response and provide detailed information about tumor growth and degeneration. In hamsters, calprotectin-positive inflammatory cells (heterophils and macrophages) were found in abundance; particularly surrounding necrotic areas in carcinomas and T cells were significantly increased in sarcomas, when these had been treated with a granulocyte-macrophage colony-stimulating factor-producing virus, suggesting a possible link between oncolysis, necrosis (seen as a hypointense core in MRI) and/or immune response. Our study indicates that both MRI and MRS could be useful in the estimation of oncolytic adenovirus efficacy at early time points after treatment.


Subject(s)
Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy , Neuroblastoma/pathology , Neuroblastoma/therapy , Oncolytic Virotherapy , Adenoviridae , Animals , Biomarkers, Tumor/analysis , Carcinoma/pathology , Carcinoma/therapy , Cells, Cultured , Choline/analysis , Cricetinae , Fatty Acids, Unsaturated/analysis , Humans , Macrophages/immunology , Male , Necrosis , Sarcoma/pathology , Sarcoma/therapy , Taurine/analysis , Treatment Outcome
6.
Gene Ther ; 21(2): 195-204, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24305418

ABSTRACT

Oncolytic vaccinia virus is an attractive platform for immunotherapy. Oncolysis releases tumor antigens and provides co-stimulatory danger signals. However, arming the virus can improve efficacy further. CD40 ligand (CD40L, CD154) can induce apoptosis of tumor cells and it also triggers several immune mechanisms. One of these is a T-helper type 1 (Th1) response that leads to activation of cytotoxic T-cells and reduction of immune suppression. Therefore, we constructed an oncolytic vaccinia virus expressing hCD40L (vvdd-hCD40L-tdTomato), which in addition features a cDNA expressing the tdTomato fluorochrome for detection of virus, potentially important for biosafety evaluation. We show effective expression of functional CD40L both in vitro and in vivo. In a xenograft model of bladder carcinoma sensitive to CD40L treatment, we show that growth of tumors was significantly inhibited by the oncolysis and apoptosis following both intravenous and intratumoral administration. In a CD40-negative model, CD40L expression did not add potency to vaccinia oncolysis. Tumors treated with vvdd-mCD40L-tdtomato showed enhanced efficacy in a syngenic mouse model and induced recruitment of antigen-presenting cells and lymphocytes at the tumor site. In summary, oncolytic vaccinia virus coding for CD40L mediates multiple antitumor effects including oncolysis, apoptosis and induction of Th1 type T-cell responses.


Subject(s)
Antineoplastic Agents/pharmacology , CD40 Ligand/genetics , Genetic Vectors/administration & dosage , Oncolytic Virotherapy/methods , Th1 Cells/immunology , Urinary Bladder Neoplasms/therapy , Animals , Apoptosis/drug effects , CD40 Ligand/immunology , Cell Line, Tumor , Genes, Reporter , Genetic Vectors/therapeutic use , Humans , Mice , Neoplasms, Experimental , Oncolytic Viruses/genetics , Tumor Microenvironment , Xenograft Model Antitumor Assays
7.
Eur J Clin Microbiol Infect Dis ; 31(10): 2639-44, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22466934

ABSTRACT

Our aim was to test whether or not true bloodstream infections (BSI) caused by coagulase negative Staphylococci (CoNS) can be distinguished from blood culture contaminants based on simple clinical and laboratory parameters. Patients with blood cultures positive for CoNS (n = 471) were categorized into community acquired infection (CAI), hospital acquired infection (HAI), infections in patients with haematological conditions (HAEI), or culture contaminants (CON) based on the judgement of a clinician. The cases were further analyzed according to widely accepted criteria for true BSI and whether or not vancomycin treatment was initiated. Simple clinical and laboratory parameters, surgical procedures, mortality, central venous catheters, and other foreign materials were registered. Our study demonstrates that the decision about the significance of positive blood culture finding made by the clinician may differ from that indicated by accepted criteria for BSI. Simple clinical findings such as heart rate, body temperature, or systolic blood pressure may not distinguish a culture contaminant from true infections. In addition, the laboratory parameters were surprisingly similar in the different patient cohorts. A blood culture positive for CoNS remains a clinical challenge; our study demonstrates that judging the significance of the finding is difficult.


Subject(s)
Bacteremia/diagnosis , Staphylococcal Infections/diagnosis , Staphylococcus/pathogenicity , Vancomycin/therapeutic use , Adult , Aged , Aged, 80 and over , Bacteremia/drug therapy , Bacteremia/microbiology , Bacteremia/mortality , Blood Pressure , Body Temperature , Central Venous Catheters/adverse effects , Coagulase , Community-Acquired Infections/drug therapy , Community-Acquired Infections/microbiology , Community-Acquired Infections/mortality , Cross Infection/drug therapy , Cross Infection/microbiology , Cross Infection/mortality , Diagnosis, Differential , Female , Gentian Violet , Hematologic Diseases/microbiology , Humans , Male , Middle Aged , Phenazines , Retrospective Studies , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Staphylococcus/enzymology , Vancomycin/administration & dosage
8.
Med Mycol ; 48(3): 458-65, 2010 May.
Article in English | MEDLINE | ID: mdl-19672782

ABSTRACT

Deep, respiratory tract and ear infections due to Microascaceae (Pseudallescheria, Scedosporium, Microascus or Scopulariopsis) were studied nationwide in Finland during 1993-2002. The data were based on 52,000 fungal cultures that represented about 50% of all such specimens in Finland and included all Finnish cases of profound immunosuppression. There were 39 cases that were re-evaluated as clinically significant, i.e., three pneumonias, two deep pedal infections and five wound infections, 11 sinusitis and 18 ear infections. The pedal infections and most pneumonias occurred in immunocompromised patients. Most cases, except the ear infections, were due to Pseudallescheria boydii. Two patients had lethal P. boydii pneumonia and a deep P. boydii infection of the foot contributed to a third lethal case. Two of the patients with lethal outcomes had received an allogeneic haematopoietic stem cell transplantation (AHSCT). Two patients with haematological malignancies were cured of deep site infections by a prolonged course of itraconazole. Wound, sinus and ear infections were cured or improved by local surgery or topical therapy. There were 0.8-1.7 cases of any type of infection per million inhabitants per year (MY) and 3.4 cases/1000 AHSCT. Mortality associated with Microascaceae in any type of patient was 0.06-0.12 MY.


Subject(s)
Ascomycota/isolation & purification , Mycoses/epidemiology , Mycoses/microbiology , Otitis/epidemiology , Otitis/microbiology , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/microbiology , Administration, Topical , Adolescent , Adult , Aged , Aged, 80 and over , Antifungal Agents/administration & dosage , Child , Debridement , Female , Finland/epidemiology , Humans , Immunocompromised Host , Male , Middle Aged , Mycoses/mortality , Mycoses/therapy , Risk Factors , Treatment Outcome , Young Adult
9.
Epidemiol Infect ; 138(7): 1004-11, 2010 Jul.
Article in English | MEDLINE | ID: mdl-19887016

ABSTRACT

This study aimed to investigate the occurrence of complications, especially musculoskeletal symptoms, after sporadic Campylobacter jejuni enteritis of domestic origin in Finland. This multi-centre cross-sectional study was conducted during a seasonal peak in 2002. Questionnaires were sent to Campylobacter-positive patients, representing different geographical areas, 2 months after collection of positive stool samples. Medical records were viewed in several cases. Besides antimicrobial susceptibility testing C. jejuni isolates were serotyped. A total of 235 patients (58%) returned the questionnaire and 201 C. jejuni-positive patients were finally included in the study. Musculoskeletal symptoms associated with C. jejuni enteritis were frequent (39%); joint pain was most commonly reported (81%). The incidence of reactive arthritis was 4% and that of Achilles enthesopathy and/or heel pain was 9%. Stomach ache during enteritis was associated with the later development of joint pain. Antimicrobial treatment was common but did not prevent complications.


Subject(s)
Campylobacter Infections/complications , Campylobacter jejuni , Musculoskeletal Diseases/epidemiology , Adolescent , Adult , Child , Child, Preschool , Diarrhea/complications , Eye Diseases/complications , Eye Diseases/epidemiology , Female , Heart Diseases/complications , Heart Diseases/epidemiology , Humans , Infant , Infant, Newborn , Male , Middle Aged , Musculoskeletal Diseases/complications , Neuralgia/complications , Neuralgia/epidemiology , Paresthesia/complications , Paresthesia/epidemiology , Self Disclosure , Surveys and Questionnaires , Urologic Diseases/complications , Urologic Diseases/epidemiology , Young Adult
10.
Clin Nephrol ; 71(5): 501-7, 2009 May.
Article in English | MEDLINE | ID: mdl-19473609

ABSTRACT

AIMS: The significance of biofilm formation for the clinical picture of urinary tract infections (UTI) is largely unknown. We wanted to find out whether Escherichia coli (E. coli) strains isolated from UTI patients differ in their ability to form biofilms and whether this ability is associated with the clinical presentation of UTI. MATERIAL AND METHODS: 70 E. coli strains were isolated from patients with cystitis (43 strains), pyelonephritis (11 strains) and urosepsis (16 strains) and biofilm formation was assessed on polystyrene microtiter plates by measuring the optical density (OD) of the attached material after 72 h of incubation and crystal violet staining of the bacteria. The formation of organized biofilm structures and the viability of the attached bacteria were verified by scanning electron microscopy and confocal scanning laser microscopy in a subsample of 22 strains. RESULTS: 31% of the E. coli strains formed a biofilm. The strains isolated from patients with pyelonephritis had higher ODs than those from patients with cystitis (difference of the means 0.19, 95% confidence limits (CL) 0.06 - 0.32, p = 0.02). The E. coli strains susceptible to antibiotics had higher ODs than the resistant strains (difference of the means 0.21, 95% CL 0.03 - 0.27, p = 0.016). CONCLUSIONS: The ability of bacteria to persist and grow in a biofilm seems to be one of the important factors in both the resistance to antibiotics and the severity of urinary tract inflammation.


Subject(s)
Biofilms/growth & development , Escherichia coli Infections/microbiology , Escherichia coli/physiology , Urinary Tract Infections/microbiology , Adolescent , Adult , Child , Child, Preschool , Colony Count, Microbial , Escherichia coli/isolation & purification , Escherichia coli/ultrastructure , Escherichia coli Infections/pathology , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Male , Microscopy, Confocal , Microscopy, Electron, Scanning , Middle Aged , Urinary Tract Infections/pathology , Urine/microbiology , Urothelium/microbiology , Urothelium/ultrastructure , Young Adult
11.
Eur J Clin Microbiol Infect Dis ; 28(3): 301-3, 2009 Mar.
Article in English | MEDLINE | ID: mdl-18763001

ABSTRACT

The effect of anti-neoplastic agents on the growth of microorganisms was studied in vitro using aerobic BacT/Alert standard and FAN bottles as the culture media. A 50% longer incubation period to detect microbial growth compared to the control group was interpreted as growth inhibition. Idarubicin inhibited the growth of all of the five gram-positive cocci, one of five gram-negative rods and one of three yeast strains studied in the standard bottles but not in the FAN bottles. Candida glabrata was the most sensitive strain. Its growth was inhibited in the presence of idarubicin at a concentration of 1 micromol/l.


Subject(s)
Bacteria/drug effects , Blood/microbiology , Fungi/drug effects , Growth Inhibitors/pharmacology , Idarubicin/pharmacology , Bacteria/growth & development , Fungi/growth & development , Humans
12.
Epidemiol Infect ; 133(4): 593-601, 2005 Aug.
Article in English | MEDLINE | ID: mdl-16050503

ABSTRACT

In August 1998, an outbreak of campylobacteriosis occurred in one municipality in northern Finland. A 10% random sample of residents (population 15 000) was selected through the National Population Registry for a survey conducted by using postal questionnaires. Cases were defined as residents of the municipality with onset of acute gastroenteritis from 1 to 20 August 1998. Of 1167 respondents (response rate 78%), 218 (18.7%) met the case definition. Drinking non-chlorinated municipal tap water was strongly associated with illness (OR 34.4). The estimated total number of ill persons was 2700. Campylobacter jejuni was isolated from stool samples of 45 (61%) out of 74 patients tested. All five isolates tested had indistinguishable PFGE patterns. Water samples were negative for campylobacter and coliforms. Epidemiological and environmental evidence suggested mains repair as the source of contamination. Non-chlorinated ground-water systems may be susceptible to contamination and can cause large outbreaks.


Subject(s)
Campylobacter Infections/epidemiology , Campylobacter jejuni/isolation & purification , Disease Outbreaks , Gastroenteritis/epidemiology , Gastroenteritis/microbiology , Water Microbiology , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Campylobacter Infections/diagnosis , Child , Child, Preschool , Confidence Intervals , Female , Finland/epidemiology , Humans , Incidence , Male , Middle Aged , Odds Ratio , Probability , Registries , Risk Assessment , Sex Distribution , Surveys and Questionnaires , Water Supply
13.
Allergy ; 58(8): 767-71, 2003 Aug.
Article in English | MEDLINE | ID: mdl-12859556

ABSTRACT

BACKGROUND: Viral cold is thought to be the major contributing factor in the pathogenesis of sinusitis, as it causes ostiomeatal obstruction. The aim was to evaluate whether paranasal sinus functioning during viral colds is similar in subjects with and without allergic rhinitis. METHODS: Forty-eight volunteers were examined during an early (2-4 days) natural cold and again 3 weeks later. The examinations included computed tomography (CT) scans, nasal mucosal biopsies, and viral and bacterial specimens. Subjects with positive skin prick tests and persistent or intermittent rhinitis were considered to have allergic immunoglobulin E (IgE)-mediated rhinitis. In addition, specific IgE antibodies to staphylococcal enterotoxin B (SEB) were measured. RESULTS: Nine subjects (19%) had allergic rhinitis. The allergic subjects were significantly more often IgE sensitized to SEB than the nonallergic subjects (33%vs 3%, P = 0.02). Viral etiology of the cold was identified in 32 (67%) subjects. The subjects with allergic rhinitis had significantly higher CT scores compared with nonallergic subjects during the colds (median (range) scores 16 (6-22) vs 6 (0-17), P = 0.004). In both groups, the median scores declined markedly during convalescence, but the difference remained significant (P = 0.009). Among the allergic subjects, those who were IgE sensitized to SEB tended to have the highest CT scores [median (range) 16 (16-22)]. Total serum IgE and the nasal subepithelial eosinophil counts correlated with the CT scores during the cold (rs = 0.38, P = 0.008 and rs = 0.46, P = 0.001, respectively). CONCLUSIONS: Subjects with allergic IgE-mediated rhinitis had more severe paranasal sinus changes in CT scans than nonallergic subjects during viral colds. These changes indicate impaired sinus functioning and may increase the risk of bacterial sinusitis.


Subject(s)
Common Cold/complications , Nasal Mucosa/pathology , Paranasal Sinuses/diagnostic imaging , Rhinitis, Allergic, Perennial/complications , Rhinitis, Allergic, Perennial/diagnostic imaging , Rhinitis, Allergic, Seasonal/complications , Rhinitis, Allergic, Seasonal/diagnostic imaging , Adult , Common Cold/virology , Female , Humans , Immunoglobulin E/blood , Male , Rhinitis, Allergic, Perennial/immunology , Rhinitis, Allergic, Perennial/pathology , Rhinitis, Allergic, Seasonal/immunology , Rhinitis, Allergic, Seasonal/pathology , Sinusitis/etiology , Tomography, X-Ray Computed
14.
Clin Exp Immunol ; 131(1): 138-42, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12519397

ABSTRACT

Knowledge of the virus-induced immune response is important in understanding the pathophysiology of respiratory virus infections. Data on the cellular immune response is still limited and based mainly on experimental studies. Natural colds may differ in their pathophysiology from experimentally induced ones. To evaluate the inflammatory cell responses in the upper respiratory tract during natural colds we counted the number of lymphocytes, mast cells and macrophages in the nasal mucosa. Nasal biopsies were taken from 22 adult volunteers during the acute (2-4 days of symptoms) and convalescent phases (day 21) of the cold, and the numbers of cells were counted with immunohistochemical methods. Viral aetiology was identified in 14 (64%) subjects by using viral isolation, antigen detection and rhino-polymerase chain reaction assays. The number of T lymphocytes was increased in the nasal epithelium and that of T and B lymphocytes and mast cells in the subepithelial layer in the acute phase compared to the convalescent phase. Intraepithelial T lymphocyte counts were significantly higher in the subjects who had a proven viral infection or a finding of pathogenic bacteria in the nasopharynx compared to the subjects without such findings (P = 0.005 and P = 0.04, respectively). Contrary to the earlier experimental studies, we found that viruses cause accumulation of T and B lymphocytes and mast cells during the first days of a symptomatic naturally acquired respiratory infection.


Subject(s)
Common Cold/immunology , Community-Acquired Infections/immunology , Lymphocytes/immunology , Mast Cells/immunology , Nasal Mucosa/immunology , Acute Disease , Adult , B-Lymphocytes/immunology , Cell Count , Humans , Lymphocyte Count , Macrophages/immunology , Statistics, Nonparametric , T-Lymphocytes/immunology
15.
IEEE Trans Neural Netw ; 13(4): 841-53, 2002.
Article in English | MEDLINE | ID: mdl-18244480

ABSTRACT

Development of content-based image retrieval (CBIR) techniques has suffered from the lack of standardized ways for describing visual image content. Luckily, the MPEG-7 international standard is now emerging as both a general framework for content description and a collection of specific agreed-upon content descriptors. We have developed a neural, self-organizing technique for CBIR. Our system is named PicSOM and it is based on pictorial examples and relevance feedback (RF). The name stems from "picture" and the self-organizing map (SOM). The PicSOM system is implemented by using tree structured SOMs. In this paper, we apply the visual content descriptors provided by MPEG-7 in the PicSOM system and compare our own image indexing technique with a reference system based on vector quantization (VQ). The results of our experiments show that the MPEG-7-defined content descriptors can be used as such in the PicSOM system even though Euclidean distance calculation, inherently used in the PicSOM system, is not optimal for all of them. Also, the results indicate that the PicSOM technique is a bit slower than the reference system in starting to find relevant images. However, when the strong RF mechanism of PicSOM begins to function, its retrieval precision exceeds that of the reference system.

16.
BJOG ; 108(8): 875-81, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11510716

ABSTRACT

OBJECTIVE: To determine the value of combinations of cervical interleukin-6 (IL-6), cervical interleukin-8 (IL-8), the phosphorylated isoform of insulin-like growth-factor binding protein-1 (IGFBP-1), and cervical ultrasonography in the prediction of preterm birth. DESIGN: Prospective follow up. SETTING: Oulu University Hospital maternity clinic from February 1997 to July 1998. POPULATION: Women with singleton pregnancies (n = 77), referred from outpatient clinics at 22-32 weeks of gestation with symptoms (uterine contractions) or signs (cervical change) of threatened preterm birth. Symptomless women (n = 78) matched for gestational age, parity and maternal age at recruitment were studied as a reference group. METHODS: A urine sample for bacterial culture was collected, and cervical swab samples for assays of interleukin-6 and -8 and phoshorylated IGFBP-1 were taken before digital cervical examination. A Pap smear for analysis of bacterial vaginosis and samples for analysis of chlamydia and streptococci were also obtained. Cervical measurements were made by transvaginal ultrasonography. The same sampling and cervical measurement were repeated twice at two-week intervals. The cutoff values of the markers were determined by receiver-operating characteristic curve analysis. MAIN OUTCOME MEASURE: Preterm birth (<37 weeks). RESULTS: The preterm birth (<37 weeks) rate for women in the study group was 16% (12/77). The cervical interleukin-6 cutoff value (61 ng/L) at first visit had a sensitivity of 73% and a specificity of 61% in predicting preterm birth, with a positive likelihood ratio (LR+ ) of 1.9 (95% CI 1.2-3.0). An ultrasonographically measured cervical index value of > 0.36 at recruitment predicted preterm birth in 25% (5/20) of the study group compared with 9% (5/54); LR+ 2.2 (95% CI 1.03-4.7). Cervical phosphorylated IGFBP-1 > 6.4 microg/L [LR+ 1.8 (95% CI 0.7-2.9)], interleukin-8 > 3739 ng/L [LR+ 1.4 (95% CI 0.9-2.4)], and ultrasonograpic cervical length < 29.3 mm [LR+ 2.7 (95% CI 0.8-9.7)] increased the risk of preterm birth. According to the logistic regression model, a combination of IL-6, and IL-8 and cervical index increased the specificity to 97%, but the sensitivity fell to 30% in detecting preterm birth. There was a significantly increased incidence of puerperal infections if phosphorylated IGFBP-1 concentrations were elevated (> 21.0 microg/L), 36% (4/11) compared with 4.6% (3/65), LR+ 6.7 (95% CI 2.7-17), the sensitivity being 67% (4/6) and the specificity 90% (63/70). Elevated phosphorylated IGFBP-1 concentrations (> 21.6 microg/L) were also associated with an increased risk of neonatal infections; LR+ 8.0 (95% CI 3.5-18). CONCLUSIONS: An increase in cervical IL-6 concentration and the ultrasonographically measured cervical index appear to be associated with preterm birth. A combination of these markers with measurement of cervical IL-8 appears to be the best predictor of preterm birth. Neither the sensitivity nor specificity of the tests used in this study are good enough to predict preterm birth for clinical decision making. Cervical phosphorylated IGFBP-1 seems to be a marker of puerperal and neonatal infectious morbidity in cases of threatened preterm delivery, suggesting early tissue degradation at the choriodecidual interface.


Subject(s)
Insulin-Like Growth Factor Binding Protein 1/metabolism , Interleukin-6/metabolism , Interleukin-8/metabolism , Obstetric Labor, Premature/diagnosis , Ultrasonography, Prenatal/standards , Adult , Biomarkers , Case-Control Studies , Cervix Uteri/metabolism , Female , Follow-Up Studies , Humans , Longitudinal Studies , Obstetric Labor, Premature/metabolism , Pregnancy , Prospective Studies , Sensitivity and Specificity
17.
BMJ ; 322(7302): 1571, 2001 Jun 30.
Article in English | MEDLINE | ID: mdl-11431298

ABSTRACT

OBJECTIVE: To determine whether recurrences of urinary tract infection can be prevented with cranberry-lingonberry juice or with Lactobacillus GG drink. DESIGN: Open, randomised controlled 12 month follow up trial. SETTING: Health centres for university students and staff of university hospital. PARTICIPANTS: 150 women with urinary tract infection caused by Escherichia coli randomly allocated into three groups. INTERVENTIONS: 50 ml of cranberry-lingonberry juice concentrate daily for six months or 100 ml of lactobacillus drink five days a week for one year, or no intervention. MAIN OUTCOME MEASURE: First recurrence of symptomatic urinary tract infection, defined as bacterial growth >/=10(5 )colony forming units/ml in a clean voided midstream urine specimen. RESULTS: The cumulative rate of first recurrence of urinary tract infection during the 12 month follow up differed significantly between the groups (P=0.048). At six months, eight (16%) women in the cranberry group, 19 (39%) in the lactobacillus group, and 18 (36%) in the control group had had at least one recurrence. This is a 20% reduction in absolute risk in the cranberry group compared with the control group (95% confidence interval 3% to 36%, P=0.023, number needed to treat=5, 95% confidence interval 3 to 34). CONCLUSION: Regular drinking of cranberry juice but not lactobacillus seems to reduce the recurrence of urinary tract infection.


Subject(s)
Beverages , Escherichia coli Infections/prevention & control , Fruit , Lactobacillus , Urinary Tract Infections/prevention & control , Adult , Female , Follow-Up Studies , Humans , Middle Aged , Recurrence , Urinary Tract Infections/microbiology
18.
Clin Infect Dis ; 32(8): 1141-54, 2001 Apr 15.
Article in English | MEDLINE | ID: mdl-11283803

ABSTRACT

To determine the etiology of community-acquired pneumonia in the adult population of a defined area, specific antibody responses in paired serum samples, levels of circulating pneumococcal immune complexes in serum samples, and pneumococcal antigen in urine were measured. Samples (304 paired serum samples and 300 acute urine samples) were obtained from 345 patients > or =15 years old with community-acquired, radiologically confirmed pneumonia, which comprised all cases in the population of 4 municipalities in eastern Finland during 1 year. Specific infecting organisms were identified in 183 patients (including 49 with mixed infection), as follows: Streptococcus pneumoniae, 125 patients; Haemophilus influenzae, 12; Moraxella catarrhalis, 8; chlamydiae, 37 (of which, Chlamydia pneumoniae, 30); Mycoplasma pneumoniae, 30; and virus species, 27. The proportion of patients with pneumococcal infections increased and of those with Mycoplasma infections decreased with age, but for each age group, the etiologic profile was similar among inpatients and among outpatients. S. pneumoniae was the most important etiologic agent. The annual incidence of pneumococcal pneumonia per 1000 inhabitants aged > or =60 years was 8.0.


Subject(s)
Community-Acquired Infections/microbiology , Community-Acquired Infections/virology , Pneumonia, Bacterial/microbiology , Pneumonia, Viral/virology , Adolescent , Adult , Age Factors , Cities , Community-Acquired Infections/drug therapy , Community-Acquired Infections/mortality , Demography , Female , Finland/epidemiology , Hospitalization , Humans , Incidence , Male , Middle Aged , Pneumonia, Bacterial/drug therapy , Pneumonia, Bacterial/epidemiology , Pneumonia, Bacterial/mortality , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Pneumonia, Viral/mortality , Sex Factors , Survivors
19.
J Fam Pract ; 50(1): 26-31, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11195477

ABSTRACT

BACKGROUND: We evaluated whether the symptoms and signs and radiologic findings during a common cold are similar in patients who have and have not suffered from recurrent sinusitis. METHODS: We recruited 2 series of volunteer cases from February 1, 1996, to December 31, 1996. Twenty-three adults who claimed to have suffered from recurrent sinusitis and 25 who had never had sinusitis were examined during the period of a self-diagnosed cold of 48 to 96 hours' duration and again after 21 days. Symptom scores were recorded, nasoendoscopy and computed tomography scans were performed, and viral and bacterial specimens were taken. RESULTS: The patients with a history of sinusitis had significantly higher symptom scores than the control patients (P=.04) and had radiologic sinusitislike changes more often (65% [15] vs 36% [9]; difference 29% [95% confidence interval, 2%-56%]; P=.04). The viral etiology of the common cold (verified in 67% of the episodes) was similar in both groups. Pathogenic bacteria were isolated from the middle meatus in 24% (6) of the control patients and only 9% (2) of the sinusitis-prone patients (P=.15). On the basis of the symptomatology, radiologic findings, and bacterial cultures only 2 patients in the sinusitis-prone group should have been treated with antimicrobials. CONCLUSIONS: Some patients are susceptible to both sinusitislike symptoms and radiologic findings during viral common colds. This may cause them to consult their physicians earlier and more often during viral colds, which may result in unnecessary antibiotic treatments. Nasopharyngeal bacteriological cultures may prove to be useful in ruling out bacterial sinusitis.


Subject(s)
Common Cold/complications , Common Cold/diagnostic imaging , Sinusitis/complications , Sinusitis/diagnostic imaging , Adult , Common Cold/microbiology , Female , Humans , Male , Recurrence , Sinusitis/drug therapy , Tomography, X-Ray Computed
20.
Antimicrob Agents Chemother ; 45(1): 166-9, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11120960

ABSTRACT

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.


Subject(s)
Fructose/pharmacology , Sorbitol/pharmacology , Streptococcus pneumoniae/growth & development , Sweetening Agents/pharmacology , Xylitol/pharmacology , Colony Count, Microbial , Culture Media , Microbial Sensitivity Tests , Streptococcal Infections/microbiology , Streptococcus pneumoniae/drug effects
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