ABSTRACT
Giant exoplanets on wide orbits have been directly imaged around young stars. If the thermal background in the mid-infrared can be mitigated, then exoplanets with lower masses can also be imaged. Here we present a ground-based mid-infrared observing approach that enables imaging low-mass temperate exoplanets around nearby stars, and in particular within the closest stellar system, α Centauri. Based on 75-80% of the best quality images from 100 h of cumulative observations, we demonstrate sensitivity to warm sub-Neptune-sized planets throughout much of the habitable zone of α Centauri A. This is an order of magnitude more sensitive than state-of-the-art exoplanet imaging mass detection limits. We also discuss a possible exoplanet or exozodiacal disk detection around α Centauri A. However, an instrumental artifact of unknown origin cannot be ruled out. These results demonstrate the feasibility of imaging rocky habitable-zone exoplanets with current and upcoming telescopes.
ABSTRACT
The risk of contracting babesiosis after a tick bite in Sweden and on the Åland Islands, Finland, is unknown. We investigated clinical and serological outcomes in people bitten by Ixodes ricinus ticks positive for Babesia species. Ticks, blood and questionnaires were obtained from study participants in Sweden and on the Åland Islands. Sixty-five of 2098 (3.1 %) ticks were positive by real-time PCR. Three Babesia species were detected, Babesia microti (n = 33), B. venatorum (n = 27) and B. capreoli (n = 5), the latter species not known to cause human infection. Half (46 %) of the Babesia PCR-positive ticks also contained Borrelia spp. Fifty-three participants bitten by a Babesia PCR-positive tick and a control group bitten by a Babesia PCR-negative tick were tested for B. microti IgG antibodies by IFA. The overall seroprevalence was 4.4 %, but there was no significant difference between the groups. None of the participants seroconverted and no participant with a Babesia PCR-positive tick sought medical care or reported symptoms suggestive of babesiosis. Given the prevalence of Babesia in I. ricinus ticks in southern Sweden and on the Åland Islands, babesiosis should be considered a possible diagnosis in symptomatic residents who seek medical care following tick exposure.
Subject(s)
Babesia/isolation & purification , Babesiosis/diagnosis , Ixodes/parasitology , Adult , Aged , Aged, 80 and over , Animals , Asymptomatic Infections , Female , Finland , Humans , Ixodes/growth & development , Larva/growth & development , Larva/parasitology , Male , Middle Aged , Nymph/growth & development , Nymph/parasitology , Seroepidemiologic Studies , Sweden , Young AdultABSTRACT
BACKGROUND: Physical activity plays an important role in public health, owing to a range of health-related benefits that it provides. Sports-related injuries are known to be an important barrier to continued physical activity. Still, the prevalence of injuries on a general population level has not yet been explored in a descriptive epidemiological investigation. The purpose of the questionnaire-based study, therefore, was to describe the prevalence of injury in a representative sample of the Danish population. METHODS: Two samples of 10,000 adults (> 15 years) and 6500 children and adolescents (7-15 years) were invited to respond to a web-based questionnaire. Of these, 3498 adults (35.0%) and 3221 children (49.6%) responded successfully. The definition of sports injury was time-loss and medical attention-based, inhibiting participants from sports activity for at least 7 days, and/or involved contact with a healthcare professional, respectively. RESULTS: Amongst adults, 642 (18.4% [95%CI: 17.1%; 19.6%]) reported to have had an injury within the past 12 months. Males reported significantly more injuries than females (difference in prevalence proportion: 9.2%-points [95%CI: 6.7%-points; 11.8%-points]). The prevalence of injuries was greatest in running (ninj = 198), football (ninj = 94) and strength training (ninj = 89). Amongst children, 621 (19.3% [95%CI: 17.9%; 20.6%]) had been injured. No difference in injury prevalence proportion existed between boys and girls. The prevalence of injuries was greatest in football (ninj = 235), handball (ninj = 86) and gymnastics (ninj = 66). CONCLUSIONS: Sports injuries seem to be very frequent in Denmark, since a total of 18.4% of the adults and 19.3% of the children reported having had one or more injuries within the past 12 months, equal to either time lost with physical activity and/or contact to the health care system.
ABSTRACT
BACKGROUND AND PURPOSE: Tick-borne encephalitis (TBE) is an infection of the central nervous system (CNS) caused by tick-borne encephalitis virus (TBEV) and transmitted by ticks, with a variety of clinical manifestations. The incidence of TBE in Europe is increasing due to an extended season of the infection and the enlargement of endemic areas. Our objectives are to provide recommendations on the prevention, diagnosis and management of TBE, based on evidence or consensus decisions. METHODS: For systematic evaluation, the literature was searched from 1970 to 2015 (including early online publications of 2016), and recommendations were based on evidence or consensus decisions of the Task Force when evidence-based data were not available. RECOMMENDATIONS: Vaccination against TBE is recommended for all age groups above 1 year in highly endemic areas (≥5 cases/100 000/year), but also for individuals at risk in areas with a lower incidence. Travellers to endemic areas should be vaccinated if their visits will include extensive outdoor activities. Post-exposure prophylaxis after a tick bite is not recommended. A case of TBE is defined by the presence of clinical signs of meningitis, meningoencephalitis or meningoencephalomyelitis with cerebrospinal fluid (CSF) pleocytosis (>5 × 106 cells/l) and the presence of specific TBEV serum immunoglobulin M (IgM) and IgG antibodies, CSF IgM antibodies or TBEV IgG seroconversion. TBEV-specific polymerase chain reaction in blood is diagnostic in the first viremic phase but it is not sensitive in the second phase of TBE with clinical manifestations of CNS inflammation. Lumbar puncture should be performed in all patients with suspected CNS infection unless there are contraindications. Imaging of the brain and spinal cord has a low sensitivity and a low specificity, but it is useful for differential diagnosis. No effective antiviral or immunomodulating therapy is available for TBE; therefore the treatment is symptomatic. Patients with a potentially life threatening meningoencephalitis or meningoencephalomyelitis should be admitted to an intensive care unit. In the case of brain oedema, analgosedation should be deepened; osmotherapy and corticosteroids are not routinely recommended. If intracranial pressure is increased, therapeutic hypothermia or decompressive craniectomy might be considered. Seizures should be treated as any other symptomatic epileptic seizures. CONCLUSIONS: Tick-borne encephalitis is a viral CNS infection that may result in long-term neurological sequelae. Since its incidence in Europe is increasing due to broadening of endemic areas and prolongation of the tick activity season, the health burden of TBE is enlarging. There is no effective antiviral treatment for TBE, but the disease may be effectively prevented by vaccination.
Subject(s)
Encephalitis Viruses, Tick-Borne , Encephalitis, Tick-Borne/diagnosis , Encephalitis, Tick-Borne/prevention & control , Encephalitis, Tick-Borne/therapy , Vaccination , Consensus , Diagnosis, Differential , Europe , Humans , Immunoglobulin M , MaleABSTRACT
Combination therapy is recommended for infections with carbapenemase-producing Klebsiella pneumoniae. However, limited data exist on which antibiotic combinations are the most effective. The aim of this study was to find effective antibiotic combinations against metallo-beta-lactamase-producing K. pneumoniae (MBL-KP). Two VIM- and two NDM-producing K. pneumoniae strains, all susceptible to colistin, were exposed to antibiotics at clinically relevant static concentrations during 24-h time-kill experiments. Double- and triple-antibiotic combinations of aztreonam, ciprofloxacin, colistin, daptomycin, fosfomycin, meropenem, rifampin, telavancin, tigecycline, and vancomycin were used. Synergy was defined as a ≥2 log10 decrease in CFU/ml between the combination and its most active drug after 24 h, and bactericidal effect was defined as a ≥3 log10 decrease in CFU/ml after 24 h compared with the starting inoculum. Synergistic or bactericidal activity was demonstrated for aztreonam, fosfomycin, meropenem, and rifampin in double-antibiotic combinations with colistin and also for aztreonam, fosfomycin, and rifampin in triple-antibiotic combinations with meropenem and colistin. Overall, the combination of rifampin-meropenem-colistin was the most effective regimen, demonstrating synergistic and bactericidal effects against all four strains. Meropenem-colistin, meropenem-fosfomycin, and tigecycline-colistin combinations were not bactericidal against the strains used. The findings of this and other studies indicate that there is great potential of antibiotic combinations against carbapenemase-producing K. pneumoniae. However, our results deviate to some extent from those of previous studies, which might be because most studies to date have included KPC-producing rather than MBL-producing strains. More studies addressing MBL-KP are needed.
Subject(s)
Anti-Bacterial Agents/pharmacology , Klebsiella pneumoniae/drug effects , Aminoglycosides/administration & dosage , Aminoglycosides/pharmacology , Anti-Bacterial Agents/administration & dosage , Aztreonam/administration & dosage , Aztreonam/pharmacology , Ciprofloxacin/administration & dosage , Ciprofloxacin/pharmacology , Colistin/administration & dosage , Colistin/pharmacology , Daptomycin/administration & dosage , Daptomycin/pharmacology , Drug Resistance, Multiple, Bacterial , Drug Synergism , Fosfomycin/administration & dosage , Fosfomycin/pharmacology , In Vitro Techniques , Lipoglycopeptides , Meropenem , Microbial Sensitivity Tests , Minocycline/administration & dosage , Minocycline/analogs & derivatives , Minocycline/pharmacology , Rifampin/administration & dosage , Rifampin/pharmacology , Thienamycins/administration & dosage , Thienamycins/pharmacology , Tigecycline , Vancomycin/administration & dosage , Vancomycin/pharmacology , beta-Lactamases/metabolismABSTRACT
Patients seeking medical care with erythema migrans or flu-like symptoms after suspected or observed tick bite in the southeast of Sweden and previously investigated for Borrelia spp. and/or Anaplasma sp. were retrospectively examined for serological evidence of rickettsial infection (Study 1). Twenty of 206 patients had IgG and/or IgM antibodies to Rickettsia spp. equal to or higher than the cut-off titre of 1:64. Seven of these 20 patients showed seroconversion indicative of recent or current infection and 13 patients had titres compatible with past infection, of which five patients were judged as probable infection. Of 19 patients with medical records, 11 were positive for Borrelia spp. as well, and for Anaplasma sp., one was judged as positive. Five of the 19 patients had antibodies against all three pathogens. Erythema migrans or rash was observed at all combinations of seroreactivity, with symptoms including fever, muscle pain, headache and respiratory problems. The results were compared by screening an additional 159 patients (Study 2) primarily sampled for the analysis of Borrelia spp. or Mycoplasma pneumoniae. Sixteen of these patients were seroreactive for Rickettsia spp., of which five were judged as recent or current infection. Symptoms of arthritis, fever, cough and rash were predominant. In 80 blood donors without clinical symptoms, approximately 1 % were seroreactive for Rickettsia spp., interpreted as past infection. The study shows that both single and co-infections do occur, which illustrate the complexity in the clinical picture and a need for further studies to fully understand how these patients should best be treated.
Subject(s)
Antibodies, Bacterial/blood , Rickettsiaceae Infections/epidemiology , Rickettsieae/immunology , Tick-Borne Diseases/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Anaplasma/immunology , Borrelia/immunology , Comorbidity , Female , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Middle Aged , Rickettsiaceae Infections/immunology , Rickettsiaceae Infections/pathology , Seroepidemiologic Studies , Sweden/epidemiology , Tick-Borne Diseases/immunology , Tick-Borne Diseases/pathology , Young AdultABSTRACT
We studied retrospectively the medical records of all patients (n = 150) diagnosed, by cerebrospinal fluid (CSF) analysis, with neuroborreliosis (NB) in Jönköping County, Sweden during 2000-2005. The number of NB cases increased from 5/100,000 to 10/100,000 inhabitants/year. In 17% of the patients, anti-Borrelia antibodies were found in CSF but not in serum at the time of diagnosis. Facial palsy, headache and fever were frequent manifestations in children, whereas unspecific muscle and joint pain were the most commonly reported symptoms in older patients. Post-treatment symptoms persisting for more than 6 months occurred in 13%, and the patients concerned were significantly older, had longer-lasting symptoms prior to treatment, had higher levels of Borrelia-specific IgG in CSF, and more often had radiculitis. The total cost of NB-related healthcare was estimated to be euro500,000 for the entire study group (euro3300 per patient), and the cost of social benefits was estimated to be euro134,000 (euro2000 per patient). CSF analysis is necessary for the diagnosis of NB, because some patients develop antibodies in serum later than in CSF. Early diagnosis of borreliosis would result in reduced human suffering and in economic gain.
Subject(s)
Endemic Diseases/economics , Health Care Costs , Lyme Neuroborreliosis/economics , Lyme Neuroborreliosis/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Bacterial/blood , Antibodies, Bacterial/cerebrospinal fluid , Child , Child, Preschool , Female , Humans , Incidence , Infant , Infant, Newborn , Lyme Neuroborreliosis/diagnosis , Lyme Neuroborreliosis/pathology , Male , Middle Aged , Retrospective Studies , Sweden/epidemiology , Young AdultABSTRACT
We studied the T-cell reactivity to overlapping peptides of B. garinii OspA, in order to locate possible immunodominant T-cell epitopes in neuroborreliosis. Cells from cerebrospinal fluid (CSF) and blood from 39 patients with neuroborreliosis and 31 controls were stimulated with 31 overlapping peptides, and interferon-gamma secreting cells were detected by ELISPOT. The peptides OspA(17-36), OspA(49-68), OspA(105-124), OspA(137-156), OspA(193-212) and OspA(233-252) showed the highest frequency of positive responses, being positive in CSF from 38% to 50% of patients with neuroborreliosis. These peptides also elicited higher responses in CSF compared with controls (P = 0.004). CSF cells more often showed positive responses to these peptides than blood cells (P = 0.001), in line with a compartmentalization to the central nervous system. Thus, a set of potential T-cell epitopes were identified in CSF cells from patients with neuroborreliosis. Further studies may reveal whether these epitopes can be used diagnostically and studies involving HLA interactions may show their possible pathogenetic importance.
Subject(s)
Antigens, Bacterial/immunology , Antigens, Surface/immunology , Bacterial Outer Membrane Proteins/immunology , Bacterial Vaccines/immunology , Borrelia burgdorferi Group/immunology , Epitopes, T-Lymphocyte/immunology , Leukocytes, Mononuclear/immunology , Lipoproteins/immunology , Lyme Neuroborreliosis/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Bacterial/blood , Antigens, Bacterial/metabolism , Antigens, Surface/metabolism , Bacterial Outer Membrane Proteins/metabolism , Bacterial Vaccines/metabolism , Child , Child, Preschool , Epitopes, T-Lymphocyte/metabolism , Female , Humans , Interferon-gamma/biosynthesis , Interferon-gamma/immunology , Leukocytes, Mononuclear/metabolism , Leukocytes, Mononuclear/microbiology , Lipoproteins/metabolism , Lyme Neuroborreliosis/microbiology , Male , Middle Aged , Peptides/immunology , Peptides/metabolism , Young AdultABSTRACT
BACKGROUND: Borrelia infections, especially chronic neuroborreliosis (NB), may cause considerable diagnostic problems. This diagnosis is based on symptoms and findings in the cerebrospinal fluid but is not always conclusive. PURPOSE: To evaluate brain magnetic resonance imaging (MRI) in chronic NB, to compare the findings with healthy controls, and to correlate MRI findings with disease duration. MATERIAL AND METHODS: Sixteen well-characterized patients with chronic NB and 16 matched controls were examined in a 1.5T scanner with a standard head coil. T1- (with and without gadolinium), T2-, and diffusion-weighted imaging plus fluid-attenuated inversion recovery (FLAIR) imaging were used. RESULTS: White matter lesions and lesions in the basal ganglia were seen in 12 patients and 10 controls (no significant difference). Subependymal lesions were detected in patients down to the age of 25 and in the controls down to the age of 43. The number of lesions was correlated to age both in patients (rho = 0.83, P<0.01) and in controls (rho = 0.61, P<0.05), but not to the duration of disease. Most lesions were detected with FLAIR, but many also with T2-weighted imaging. CONCLUSION: A number of MRI findings were detected in patients with chronic NB, although the findings were unspecific when compared with matched controls and did not correlate with disease duration. However, subependymal lesions may constitute a potential finding in chronic NB.
Subject(s)
Brain Diseases/pathology , Lyme Neuroborreliosis/pathology , Magnetic Resonance Imaging , Adult , Age Factors , Aged , Aged, 80 and over , Brain Diseases/complications , Brain Diseases/microbiology , Case-Control Studies , Chronic Disease , Female , Humans , Lyme Neuroborreliosis/complications , Male , Middle Aged , Time FactorsABSTRACT
Lyme borreliosis (LB) can, despite adequate antibiotic treatment, develop into a chronic condition with persisting symptoms such as musculoskeletal pain, subjective alteration of cognition and fatigue. The mechanism behind this is unclear, but it has been postulated that an aberrant immunological response might be the cause. In this study we investigated the expression of the T helper 1 (Th1) marker interleukin (IL)-12Rbeta2, the marker for T regulatory cells, forkhead box P3 (FoxP3) and the cytokine profile in patients with a history of chronic LB, subacute LB, previously Borrelia-exposed asymptomatic individuals and healthy controls. Fifty-four individuals (12 chronic LB, 14 subacute LB, 14 asymptomatic individuals and 14 healthy controls) were included in the study and provided a blood sample. Mononuclear cells were separated from the blood and stimulated with antigens. The IL-12Rbeta2 and FoxP3 mRNA expression was analysed with real-time reverse transcription-polymerase chain reaction (RT-PCR). The protein expression of IL-12Rbeta2 on CD3(+), CD4(+), CD8(+) and CD56(+) cells was assessed by flow cytometry. Furthermore, the secretion of interferon (IFN)-gamma, IL-4, IL-5, IL-10, IL-12p70 and IL-13 was analysed by enzyme-linked immunospot (ELISPOT) and/or enzyme-linked immunosorbent assay (ELISA). Chronic LB patients displayed a lower expression of Borrelia-specific IL-12Rbeta2 on CD8(+) cells and also a lower number of Borrelia-specific IFN-gamma-secreting cells compared to asymptomatic individuals. Furthermore, chronic LB patients had higher amounts of Borrelia-specific FoxP3 mRNA than healthy controls. We speculate that this may indicate that a strong Th1 response is of importance for a positive outcome of a Borrelia infection. In addition, regulatory T cells might also play a role, by immunosuppression, in the development of chronic LB.
Subject(s)
Borrelia burgdorferi , Forkhead Transcription Factors/metabolism , Interferon-gamma/metabolism , Interleukin-12 Receptor beta 2 Subunit/metabolism , Lyme Disease/immunology , Adult , Aged , Aged, 80 and over , Antibodies, Bacterial/blood , Antibodies, Bacterial/cerebrospinal fluid , CD8-Positive T-Lymphocytes/immunology , Case-Control Studies , Chronic Disease , Enzyme-Linked Immunosorbent Assay/methods , Female , Flow Cytometry , Forkhead Transcription Factors/analysis , Forkhead Transcription Factors/genetics , Humans , Interferon-gamma/immunology , Interleukin-10/analysis , Interleukin-12 Receptor beta 2 Subunit/analysis , Interleukin-12 Receptor beta 2 Subunit/genetics , Lyme Disease/metabolism , Lyme Disease/pathology , Lyme Neuroborreliosis , Male , Middle Aged , Reverse Transcriptase Polymerase Chain Reaction , Statistics, NonparametricABSTRACT
Lyme borreliosis and human granulocytic ehrlichiosis are tick-borne diseases caused by Borrelia burgdorferi and Anaplasma phagocytophilum, respectively. Infection with A. phagocytophilum has been observed to induce immunosuppression and animal studies suggest that the bacteria might also have prolonged inhibitory effects on immune cells. The aim of this study was to investigate the cytokine secretion in patients exposed previously to A. phagocytophilum and currently infected with B. burgdorferi compared with patients infected with B. burgdorferi and seronegative for A. phagocytophilum. Eight patients with erythema migrans and antibodies against A. phagocytophilum, 15 patients with erythema migrans and negative A. phagocytophilum serology and 15 non-exposed healthy individuals were included in the study. Blood mononuclear cells were stimulated with Borrelia-antigen and the number of cytokine [interleukin (IL)-4, IL-5, IL-12, IL-13 and interferon (IFN)-gamma]-secreting cells was detected by enzyme-linked immunospot (ELISPOT). This study shows that patients with a previous exposure to A. phagocytophilum and a current infection with B. burgdorferi have a lower number of Borrelia-specific cells secreting IL-12 compared to Ap seronegative patients infected with B. burgdorferi (P < 0.001), indicating impairment in the ability to mount strong Th1-responses. We suggest that this mirrors a reduced Th1 response caused by A. phagocytophilum which could influence the outcome of the Borrelia infection and, speculatively, may also have implications in other conditions.
Subject(s)
Anaplasma phagocytophilum/immunology , Ehrlichiosis/immunology , Interleukin-12/immunology , Lyme Disease/immunology , Adolescent , Adult , Aged , Antibodies, Bacterial/immunology , Enzyme-Linked Immunosorbent Assay/methods , Erythema Chronicum Migrans/immunology , Female , Granulocytes/immunology , Humans , Interferon-gamma/immunology , Interleukin-13/immunology , Interleukin-4/immunology , Interleukin-5/immunology , Male , Middle AgedABSTRACT
Innate immunity is important for early defence against borrelia spirochetes and should play a role in the clinical outcome of the infection. In order to study early cytokine responses, in vitro differentiated dendritic cells (DCs) and whole blood cells from 21 patients with different clinical outcomes of Lyme neuroborreliosis were stimulated with live borrelia spirochetes. The borrelia-induced secretion of interleukin (IL)-4, IL-10, IL-12p70, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha in DCs and IL-1beta, IL-6, IL-8, IL-10, IL-12p70, TNF-alpha, regulated upon activation normal T cell expressed and secreted (RANTES), monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta and eotaxin in whole blood cells was measured by enzyme-linked immunospot (ELISPOT) and multiplex arrays, respectively. We found increased numbers of TNF-alpha-secreting DCs (P = 0.018) in asymptomatic seropositive individuals compared to patients with subacute neuroborreliosis and seronegative controls. Asymptomatic individuals were also found to have elevated levels of IL-12p70 (P = 0.031) in whole blood cell supernatants compared to seronegative controls. These results are in line with previous experiments using cells of the adaptive immune response, indicating that strong T helper type 1 (Th1) proinflammatory responses might be associated with a successful resolution of Lyme disease.
Subject(s)
Borrelia burgdorferi Group/immunology , Interleukin-12/biosynthesis , Lyme Neuroborreliosis/immunology , Tumor Necrosis Factor-alpha/biosynthesis , Acute Disease , Adult , Aged , Aged, 80 and over , Antigens, Surface/metabolism , Carrier State/immunology , Cells, Cultured , Chemokines/blood , Chronic Disease , Cytokines/biosynthesis , Dendritic Cells/immunology , Enzyme-Linked Immunosorbent Assay/methods , Female , Humans , Male , Middle Aged , PrognosisABSTRACT
Five commercial Borrelia serology kits available in Sweden were evaluated and compared for their diagnostic performance in sera from clinically well-characterized patient groups. With the clinically defined groups as the gold standard, i.e. without knowledge of antibody status in serum and cerebrospinal fluid, the diagnostic performance of the kits was compared and important differences in diagnostic usefulness were found. The kits from Abbot and DAKO, that often predict clinically relevant Borrelia infection and do not detect antibodies in sera from patients without strong suspicion of Borrelia infection, were considered the most useful in the population studied. This kind of validation study is an important part of good laboratory practice and should be performed by laboratories serving patient populations with varying endemicity of Borrelia.
Subject(s)
Borrelia/isolation & purification , Lyme Disease/blood , Reagent Kits, Diagnostic/standards , Antibodies, Bacterial/blood , Antibodies, Bacterial/cerebrospinal fluid , Humans , Lyme Disease/cerebrospinal fluid , Sensitivity and Specificity , SwedenABSTRACT
The immuno-pathogenetic mechanisms underlying chronic Lyme neuroborreliosis are mainly unknown. Human Borrelia burgdorferi (Bb) infection is associated with Bb-specific secretion of interferon-gamma (IFN-gamma), which may be important for the elimination of Bb, but this may also cause tissue injury. In order to increase the understanding of the pathogenic mechanisms in chronic neuroborreliosis, we investigated which cell types that secrete IFN-gamma. Blood mononuclear cells from 13 patients with neuroborreliosis and/or acrodermatitis chronicum atrophicans were stimulated with Bb antigen and the phenotypes of the induced IFN-gamma-secreting cells were analyzed with three different approaches. Cells expressing CD8 or TCRgammadelta, which both have cytolytic properties, were the main phenotypes of IFN-gamma-secreting cells, indicating that tissue injury in chronic neuroborreliosis may be mediated by cytotoxic cells.
Subject(s)
Borrelia burgdorferi/immunology , Cytotoxicity, Immunologic , Immunophenotyping , Interferon-gamma/metabolism , Leukocytes, Mononuclear/metabolism , Lyme Neuroborreliosis/immunology , Lyme Neuroborreliosis/metabolism , Adult , Aged , Antibodies, Blocking/pharmacology , Antigens, CD1/immunology , Antigens, CD1d , CD4-Positive T-Lymphocytes/chemistry , CD4-Positive T-Lymphocytes/immunology , CD56 Antigen/analysis , CD8-Positive T-Lymphocytes/chemistry , CD8-Positive T-Lymphocytes/immunology , Chronic Disease , Enzyme-Linked Immunosorbent Assay , Female , Glycoproteins/immunology , HLA Antigens/immunology , Humans , Immunomagnetic Separation , Interferon-gamma/analysis , Intracellular Fluid/chemistry , Intracellular Fluid/immunology , Intracellular Fluid/microbiology , Leukocytes, Mononuclear/chemistry , Leukocytes, Mononuclear/immunology , Lyme Neuroborreliosis/microbiology , Male , Middle Aged , Receptors, Antigen, T-Cell, gamma-delta/analysis , Receptors, Antigen, T-Cell, gamma-delta/biosynthesis , Staining and LabelingABSTRACT
OBJECTIVES: The existence of chronic neuroborreliosis is controversial. The aim of our study was to investigate the existence and kind of persistent symptoms in patients previously treated because of neurological symptoms as a result of neuroborreliosis. MATERIALS AND METHODS: A total of 106 patients with neuroborreliosis, according to established criteria, and a control group of 123 patients with Borrelia induced erythema migrans diagnosed in a general practitioner office were studied. A questionnaire was sent to patients and controls concerning their health situation. Time from onset of neurological symptoms to the questionnaire send out was 32 months (mean) for the patients with neuroborreliosis and 33 months (mean) for the controls. RESULTS: Fifty per cent of the individuals in the patient group compared with 16% of the individuals in the control group showed persistent complaints after their Borrelia infection (P < 0.0001). The most significant differences between the groups were the presence of neuropsychiatric symptoms such as headache, attention problems, memory difficulties and depression. Paresthesia, pain and persistent facial palsy was also significantly more common in patients treated because of neuroborreliosis. CONCLUSION: Our study shows that persisting neurological symptoms are common after a neuroborreliosis infection. The pathological mechanisms that lay behind the development of chronic symptoms, however, are still uncertain.
Subject(s)
Lyme Neuroborreliosis/psychology , Nervous System Diseases/epidemiology , Adult , Aged , Aged, 80 and over , Chronic Disease , Female , Follow-Up Studies , Humans , Lyme Neuroborreliosis/complications , Male , Middle Aged , Nervous System Diseases/etiology , Surveys and Questionnaires , Treatment OutcomeABSTRACT
BACKGROUND: Hepatocyte growth factor (HGF) is a heparin-binding protein with mitogenic, motogenic and morphogenic activities for various cell types. The regenerative properties of HGF have been the object of several animal and in vitro studies in recent years. OBJECTIVE: To investigate the physiological and therapeutic effects of HGF on chronic leg ulcers. METHODS: HGF in gel form was locally applied, once daily for 7 days, to 15 of 19 chronic leg ulcers in 11 elderly patients. All patients had previously been treated by conventional methods and their leg ulcers had been in stable conditions for between 1 and 14 years. Any signs of allergy, discomfort or pain were reported daily. Microcirculation perfusion in the ulcers, compared to the intact contiguous skin, was determined by laser Doppler at the beginning of the study, after 1 week and again after 3 months (in seven patients). Ulcer size and characteristics were also documented. RESULTS: It was observed that microcirculatory perfusion, which might reflect the angiogenic effect of HGF, was statistically significantly correlated (r = 0.94, p < 0.002) to ulcer area reduction in the treated ulcers. Excellent (84-100% area reduction) or partial healing (58-59%) was seen in eight out of 11 patients. No control group was included in this pilot study, which must be completed by proper control studies. CONCLUSION: This study suggests that HGF may heal chronic leg ulcers, possibly by improving the microcirculation. Proper control studies need to be performed.
Subject(s)
Hepatocyte Growth Factor/therapeutic use , Leg Ulcer/drug therapy , Wound Healing/drug effects , Aged , Chronic Disease , Female , Gels , Humans , Leg/blood supply , Leg Ulcer/physiopathology , Microcirculation/drug effects , Middle Aged , Pilot ProjectsABSTRACT
Acute serum levels of hepatocyte growth factor (HGF) were studied in 6 clinical groups with (i) gastroenteritis, (ii) skin and soft tissue infection, (iii) urinary tract infection, (iv) septicemia, (v) influenza, and (vi) chronic hepatitis C in comparison with a normal control group using an enzyme-linked immunosorbent assay method. We found that serum HGF levels were significantly higher in patients with acute infectious diseases (p < 0.0001) compared to patients with chronic viral hepatitis and healthy controls. Serum HGF and CRP levels were correlated significantly (r=0.65, p < 10(-7)). We conclude that serum HGF levels are elevated in patients with acute infectious diseases.
Subject(s)
Community-Acquired Infections/blood , Hepatocyte Growth Factor/blood , Acute Disease , Adult , Aged , Aged, 80 and over , Analysis of Variance , Biomarkers/blood , Chronic Disease , Female , Gastroenteritis/blood , Humans , Influenza, Human/blood , Male , Middle Aged , Sepsis/blood , Skin Diseases, Infectious/blood , Urinary Tract Infections/bloodABSTRACT
Hepatocyte growth factor (HGF) is a protein produced by mesenchymal cells in many organs, which can stimulate epithelial growth. An enhanced production and concentration of HGF is observed after injuries. The lung is one of the major sources of HGF. By cooling exhaled air, a condensate is formed containing molecules from bronchi and alveoli. In order to investigate HGF-concentration and time course in pneumonia, paired serum and exhaled breath condensate was collected from 10 patients with pneumonia, 10 patients with non-respiratory infections and 11 healthy controls. The concentration of HGF was measured by an immunoassay kit. In the acute phase HGF-levels in breath condensate and serum were significantly higher in the patients with pneumonia compared to the control groups. Similar concentrations in breath condensate were seen in healthy controls and in patients with non-respiratory infections. In the patients with pneumonia a decrease in serum HGF was seen already after 4-7 days while HGF values in breath condensate remained elevated even after 4-6 weeks. These results might imply local product on of HGF in the lungs and a long repair and healing process after pneumonia.
Subject(s)
Hepatocyte Growth Factor/analysis , Pneumonia/metabolism , Adult , Aged , Aged, 80 and over , Analysis of Variance , Biomarkers/analysis , Biomarkers/blood , Breath Tests , Bronchi/chemistry , Case-Control Studies , Female , Hepatocyte Growth Factor/blood , Humans , Male , Middle Aged , Pulmonary Alveoli/chemistry , Time FactorsABSTRACT
A prospective study was carried out in which brain, core and skin temperatures were studied in children with cerebral malaria (n = 23), uncomplicated malaria (n = 12) and normal children (n = 9) using the zero heat flow method. Patients with cerebral or uncomplicated malaria were admitted to the paediatric wards (mean age, 6 years 8 months +/- 2 years 8 months). Normal children, children of the investigators, of the same age group, served as controls. Parasitaemia levels were similar in the cerebral and uncomplicated malaria cases. Higher brain than core temperatures would have been expected in cerebral malaria but not in uncomplicated malaria but this was not the case in this study. There was no statistical difference in brain, core and skin temperature between cerebral and uncomplicated malaria patients. However, there was a highly significant difference between normal children and cerebral and uncomplicated malaria patients. Brain temperature was 0.02-0.2 degrees C below core temperature in all the groups with larger differences during the febrile period. Mean differences of brain minus core, brain minus skin and core minus skin between the two groups of patients were not statistically significant. There was no correlation between temperature and the level of coma or parasitaemia for cerebral and uncomplicated malaria patients. There was a positive correlation between brain and core temperature in both groups of patients during the febrile phase. Brain temperature remained lower than core temperature in cerebral and uncomplicated malaria as in normal children. Normal thermoregulation appears to be maintained in cerebral malaria.