Outpatient Antibiotic Use and Costs in Adults: A Nationwide Register-Based Study in Finland 2008-2019.

The objective of this study was to describe the prevalence of outpatient use and costs for systemic antibacterials by age and sex among adults in Finland from 2008-2019. Data from the Finnish statistical database Kelasto, containing information concerning all reimbursed medicines for 18+-year-olds during 2008-2019, were analyzed. In addition to the decreased (26%) use of systemic antibiotics, decreased use was observed in all antibiotic categories, notably including several wide-spectrum antibiotics. The use of quinolones decreased by 49% and of tetracyclines by 39%. The 10 most frequently used antibiotics covered 89% of all adult antibiotic prescriptions. Antibiotic use also decreased in every age group during the study period. Although the overall yearly costs of outpatient antibiotics during the 10-year study period decreased from EUR 36.4 million to EUR 30.7 million, the cost per prescription increased slightly. In conclusion, according to the findings of this study, concerning adults and the results of our previous study concerning children and adolescents (2008-2016), there has been a decreasing trend of outpatient antibacterial use among the whole Finnish outpatient population over the duration of nearly one decade. However, during the same time period, there has been a specific increasing trend for the Gram-negative AMR threat regarding E. coli resistance. Therefore, based on our important findings in Finland, methods other than the restriction of antibiotic use, such as new anti-infective innovations, including antibacterials, are needed as soon as possible to tackle this major global health threat-a silent pandemic.

Oral Doxycycline Compared to Intravenous Ceftriaxone in the Treatment of Lyme Neuroborreliosis: A Multicenter, Equivalence, Randomized, Open-label Trial.

BACKGROUND: Lyme neuroborreliosis (LNB) is often treated with intravenous ceftriaxone even if doxycycline is suggested to be noninferior to ceftriaxone. We evaluated the efficacy of oral doxycycline in comparison to ceftriaxone in the treatment of LNB. METHODS: Patients with neurological symptoms suggestive of LNB without other obvious reasons were recruited. The inclusion criteria were (1) production of Borrelia burgdorferi-specific antibodies in cerebrospinal fluid (CSF) or serum; (2) B. burgdorferi DNA in the CSF; or (3) an erythema migrans during the past 3 months. Participants were randomized in a 1:1 ratio to receive either oral doxycycline 100 mg twice daily for 4 weeks, or intravenous ceftriaxone 2 g daily for 3 weeks. The participants described their subjective condition with a visual analogue scale (VAS) from 0 to 10 (0 = normal; 10 = worst) before the treatment, and 4 and 12 months after the treatment. The primary outcome was the change in the VAS score at 12 months. RESULTS: Between 14 September 2012 and 28 December 2017, 210 adults with suspected LNB were assigned to receive doxycycline (n = 104) or ceftriaxone (n = 106). The per-protocol analysis comprised 82 patients with doxycycline and 84 patients with ceftriaxone. The mean change in the VAS score was -3.9 in the doxycycline group and -3.8 in the ceftriaxone group (mean difference, 0.17 [95% confidence interval, -.59 to .92], which is within the prespecified equivalence margins of -1 to 1 units). Participants in both groups improved equally. CONCLUSIONS: Oral doxycycline is equally effective as intravenous ceftriaxone in the treatment of LNB. CLINICAL TRIALS REGISTRATION: NCT01635530 and EudraCT 2012-000313-37.

Outpatient antibacterial use and costs in children and adolescents: a nationwide register-based study in Finland, 2008-16.

OBJECTIVES: To describe the prevalence of outpatient use and the costs of systemic antibacterials among children and adolescents in Finland during 2008-16 and to examine patterns of use by age and gender. METHODS: Data were retrieved from the Finnish statistical database Kelasto, based on the Finnish Prescription Registry. Data included information on dispensed reimbursed prescriptions of antibacterials for systemic use in children aged 0-17 years during 2008-16. The prevalence of antibacterial prescriptions per 1000 children and costs per prescription were calculated. RESULTS: The overall prevalence of antibacterial prescriptions decreased in the study period and was highest in 2010 (with 708 prescriptions per 1000 children) and lowest in 2016 (with 374 prescriptions per 1000 children). Children aged 1-2 years had the highest prevalence of antibacterial prescriptions. Furthermore, boys had slightly higher prevalences than girls. The 10 most commonly used antibacterial agents covered ∼97% of all prescriptions and broad-spectrum penicillins were the most commonly used antibacterials. The total costs of antibacterials decreased during the study period, but the costs per prescription increased. CONCLUSIONS: This study showed a decreasing trend in the prescribing of antibacterial drugs, regardless of age or gender. Increasing awareness of antimicrobial resistance, reimbursement status changes and pneumococcal and influenza vaccinations are possible reasons for this. Some of the antibacterial oral solutions lost their reimbursement status, but their consumption did not decrease any faster than the consumption of the substances with continuous reimbursability. It is likely that removing the reimbursement status of antibacterials has placed an extra cost burden on families and increased costs per prescription.

Evaluation of risk factors for oral infection with potential for spread in a 1-year cohort study.

OBJECTIVES: To determine the frequency of oral infection with potential for spread (OIPS) and behavioural risk factors in patients referred to a regional tertiary care-centre for OIPS assessment and clearance. MATERIALS AND METHODS: A database search of all referrals to the Oral and Maxillofacial Diseases unit of HUH in 2009 was performed. Of the 2807 referrals, 408 were due to a known or suspected OIPS. The electronic patient records of these patients were analysed for patient demographics, lifestyle factors, radiological findings and clinical oral findings. Risk factors for OIPS were analysed using logistic regression and using the significant factors in univariate analyses in the multivariate models. RESULTS: The mean age of the patients was 58 years. Most patients (n = 270, 66%) were referred due to upcoming cancer or other immunosuppressive therapy. The majority (n = 314, 77%) were diagnosed with one or more OIPS. In univariate analyses, smoking (OR 3.2, 95% CI 1.6-6.4; p = 0.0006), male gender (OR 1.7, 95% CI 1.1-2.8; p = 0.02), excessive alcohol use (OR 3.0, 95% 1.1-7.9; p = 0.03) and irregular dental care (OR 4.8, 95% CI 2.6-8.8; p < 0.0001) were risk factors for OIPS. However, in multivariate analyses, smoking was the only independent risk factor for OIPS (OR 3.6, 95% CI 1.2-11.8; p = 0.02). CONCLUSIONS: OIPS are common in patients referred for OIPS clearance, and smoking was identified as an independent behavioural risk factor for them. These findings highlight the burden of disease in this patient group and the importance of smoking cessation encouragement. CLINICAL RELEVANCE: To identify patients at increased risk of OIPS.

Subclinical inflammation associated with prolonged TIMP-1 upregulation and arterial stiffness after gestational diabetes mellitus: a hospital-based cohort study.

BACKGROUND: Gestational diabetes mellitus (GDM) has significant implications for the future health of the mother. Some clinical studies have suggested subclinical inflammation and vascular dysfunction after GDM. We aimed to study whether concentrations of high-sensitivity C-reactive protein (hsCRP), tissue inhibitor of metalloproteinase-1 (TIMP-1), matrix metalloproteinase-8 (MMP-8) and -9, as well as values of arterial stiffness differ between women with and without a history of GDM a few years after delivery. We also investigated possible effects of obesity on the results. METHODS: We studied two cohorts-120 women with a history of GDM and 120 controls-on average 3.7 years after delivery. Serum concentrations of hsCRP were determined by immunonephelometric and immunoturbidimetric methods, MMP-8 by immunofluorometric assay, and MMP-9 and TIMP-1 by enzyme-linked immunosorbent assays. Pulse wave velocity (PWV) was determined using the foot-to-foot velocity method from carotid and femoral waveforms by using a SphygmoCor device. Arterial compliance was measured non-invasively by an HDI/PulseWave™CR-2000 arterial tonometer. All 240 women were also included in subgroup analyses to study the effect of obesity on the results. Multiple linear regression analyses were performed with adjustment for confounding factors. RESULTS: PWV after pregnancy complicated by GDM was significantly higher than after normal pregnancy, 6.44 ± 0.83 (SD) vs. 6.17 ± 0.74 m/s (p = 0.009). Previous GDM was also one of the significant determinants of PWV in multiple linear regression analyses. On the other hand, compliance indices of both large (p = 0.092) and small (p = 0.681) arteries did not differ between the study cohorts. Serum TIMP-1 levels were significantly increased after previous GDM (p = 0.020). However, no differences were found in the serum levels of MMP-8, MMP-9 or hsCRP. In subgroup analyses, there were significantly higher concentrations of hsCRP (p = 0.015) and higher PWV (p < 0.001) among obese women compared with non-obese ones. CONCLUSIONS: PWV values were significantly higher after GDM compared with normoglycemic pregnancies and were associated with prolonged TIMP-1 upregulation. Cardiovascular risk factors were more common in participants with high BMI than in those with previous GDM.

Association of MMP-8 with obesity, smoking and insulin resistance.

BACKGROUND: Obesity has been recognized as a state of subclinical inflammation resulting in a loss of insulin receptors and decreased insulin sensitivity. We here studied in vivo the role of circulating matrix metalloproteinase-8 (MMP-8) among young healthy twin adults. Also, in vitro analysis of the cleavage of human insulin receptor (INSR) by MMP-8 was investigated as well its inhibition by doxycycline and other MMP-8 inhibitor, Ilomastat/GM6001, which are broad-spectrum MMP inhibitors. MATERIALS AND METHODS: We analysed serum MMP-8 levels by a time-resolved immunofluorometric assay in obese (n = 34), overweight (n = 76) and normal weight (n = 130) twin individuals. The effect of MMP-8 on INSR and the effects of synthetic MMP-8 inhibitors, doxycycline and Ilomastat/GM6001, were studied by SDS-PAGE. RESULTS: We found that in obese individuals relative to normal weight individuals, the serum MMP-8 levels and MMP-8/TIMP-1 ratio were significantly increased (P = 0·0031 and P = 0·031, respectively). Among normal weight and obese individuals, also smoking significantly increases serum MMP-8 and MMP-8/TIMP-1 ratio. In vitro, we found that INSR was degraded by MMP-8 and this was inhibited by doxycycline and Ilomastat/GM6001. CONCLUSIONS: Obesity associated with elevated circulating MMP-8 found among young adults may contribute to progression of insulin resistance by cleaving INSR. This INSR cleavage by MMP-8 can be inhibited by synthetic MMP-8 inhibitors such as doxycycline. In addition to obesity, also smoking independently explained increased MMP-8 levels. Our results suggest that MMP-8 is an essential mediator in systemic subclinical inflammatory response in obesity, and a potential drug target.

Decreased salivary matrix metalloproteinase-8 reflecting a defensive potential in juvenile parotitis.

OBJECTIVE: Matrix metalloproteinases MMP-2 and MMP-9 have been associated with juvenile parotitis. However, the role of MMP-8 has not been addressed previously. This work focuses on salivary MMP-8 and -9 levels in juvenile parotitis. METHODS: During a five-year period at Helsinki University Hospital, a tertiary care hospital, 41 patients aged 17 or under, were identified as having parotitis; from 36 of these patients, saliva samples were collected for MMP-8 IFMA (time-resolved immunofluorometric assay) analyses. Control saliva samples were collected from 34 age- and gender-matched children admitted for an elective surgery who had no history of parotitis. For comparison, salivary levels of MMP-9, tissue inhibitor of matrix metalloproteinase (TIMP-1), MMP-8/TIMP-1 ratio, human neutrophil elastase (HNE), and myeloperoxidase (MPO) were analyzed by ELISA. Additionally, salivary MMP-8 levels were compared to historical saliva samples from 18 adult gingivitis patients as well as to 10 healthy adult controls. RESULTS: The median (25%, 75% percentile) MMP-8 concentration in saliva of parotitis patients was significantly lower than MMP-8 concentration in saliva of their controls [50.4ng/ml (37.5, 72.9) vs. 148.5ng/ml (101.2, 178.5) p<0.0001] and lower than in patients with gingivitis [347.9ng/ml (242.6, 383.2) p<0.0001] or healthy adult controls [257.2ng/ml (164.9, 320.7) p<0.0001]. The MMP-8/TIMP-1 ratio was lower than in controls [0.13 (0.05-0.02) vs. 0.3 (0.17-0.46) p<0.0001]. The median MMP-9 concentration in saliva of parotitis patients was significantly higher than in controls [143.9ng/m (68.8-189.0) vs. 34.9ng/ml (16.3-87.6) p<0.0001]. Neither HNE, MPO, nor TIMP-1 alone separated the patients from the control groups. CONCLUSIONS: MMP-9 was up-regulated in juvenile parotitis saliva, suggesting that MMP-9 may play a destructive role in juvenile parotitis, as others have suggested. The present novel findings reveal a decreased salivary MMP-8 concentration, suggesting that MMP-8 may reflect in juvenile parotitis down-regulated or anti-inflammatory immune characteristics.

Changes in MMP-9 and TIMP-1 Concentrations in Cerebrospinal Fluid after 1 Week of Treatment of Childhood Bacterial Meningitis.

We explored the changes of the initially highly upgraded cerebrospinal fluid matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of MMP 1 (TIMP-1) response during recovery of childhood bacterial meningitis and their association with outcome. The sizes of these changes varied substantially, but a steeper decrease in the MMP-9 and an increase of the TIMP-1 concentrations augured a better outcome.

Predictive value of cerebrospinal fluid matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 concentrations in childhood bacterial meningitis.

BACKGROUND: Increased concentrations of matrix metalloproteinases (MMP) in cerebrospinal fluid are part of the host response in bacterial meningitis (BM). We investigated whether the concentrations of MMP-9 and the tissue inhibitor of metalloproteinase (TIMP)-1 predict the outcome in childhood BM. METHODS: Cerebrospinal fluid MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) were quantified by an enzyme-linked immunosorbent assay from 264 and 335 patients, respectively; 43 children without BM served as controls. The results were compared with previously known independent predictors of death and sequelae. RESULTS: Higher MMP-9 and TIMP-1 values distinguished the controls from the BM patients (P < 0.0001). A MMP-9 concentration >940 ng/mL proved an independent predictor of death [adjusted odds ratio: 4.03; 95% confidence interval (CI): 2.09-7.77; P < 0.0001]. If the patient additionally presented with a Glasgow Coma Score below 9, the odds increased to 13.21 (95% CI: 5.44-32.08; P < 0.0001). TIMP-1 levels correlated with the severity of sequelae (ρ: 0.30; P < 0.0001), but not with death. Its concentration above 390 ng/mL increased the likelihood of sequelae 3.43-fold (95% CI: 1·73-6·79; P = 0.0004), and up to 31.18-fold (95% CI: 4.05-239.8; P = 0.0009) if the patient also presented a Glasgow Coma Score < 12. CONCLUSIONS: Elevated cerebrospinal fluid MMP-9 and TIMP-1 values predict 2 important outcomes in childhood BM. Combined with a clinical evaluation, quantification of these indices augments the chances to identify the patients in greatest need of better treatment modalities.

Matrix metalloproteinase-8/collagenase-2 in childhood otitis media with effusion.

BACKGROUND: Matrix metalloproteinases (MMPs), gelatinases, have been associated with otitis media with effusion (OME), but the role of collagenase-2/matrix metalloproteinase-8 (MMP-8) in OME has not been studied previously. We studied the levels, isoenzyme distribution, and activation of MMP-8 in childhood OME, and also the levels of pro- and active forms of MMP-2 and -9 as well as 120 kDa gelatinase complexes were assessed. METHODS: Seventy middle ear fluid (MEF) samples were collected from 54 children with OME and classified to mucoid (n = 39) or serous (n = 31). MMPs were studied from MEF samples by time-resolved immunofluorometric assay, Western immunoblotting, and gelatin-zymography. RESULTS: MMP-8 was found in its active form in MEF of children with OME. MMP-8 levels were significantly higher in mucous relative to serous OME. The pro- or active MMP-2 and -9 were found in MEF, but no MEF type-specific differences were found. CONCLUSION: Our results suggest that MMP-8 may play a role in the pathogenesis of childhood OME. New therapeutic strategies with MMP inhibitors targeting MMP-8, but allowing MMP-8 to carry out the protective action, may play a role in the future treatment of otitis media and OME. However, further studies of this topic are needed.

Serum matrix metalloproteinases in patients resuscitated from cardiac arrest. The association with therapeutic hypothermia.

AIM: To study the systemic levels of matrix metalloproteinases (MMP) -7, -8 and -9 and their inhibitor TIMP-1 in cardiac arrest patients and the association with mild therapeutic hypothermia treatment on the serum concentration of these enzymes. METHODS: MMP-7, -8 and -9 and tissue inhibitor of metalloproteinases-1 (TIMP-1) were analysed in blood samples obtained from 51 patients resuscitated from cardiac arrest. The samples were taken at 24 and 48 h from restoration of spontaneous circulation (ROSC). The biomarker levels were compared between patients (N=51) and healthy controls (N=10) and between patients who did (N=30) and patients who did not (N=21) receive mild therapeutic hypothermia. RESULTS: MMP-7 (median 0.47 ng/ml), MMP-8 (median 31.16 ng/ml) and MMP-9 (median 253.00 ng/ml) levels were elevated and TIMP-1 levels suppressed (median 78.50 ng/ml) in cardiac arrest patients as compared with healthy controls at 24h from ROSC. Hypothermia treatment associated with attenuated elevation of MMP-9 (p=0.001) but not MMP-8 (p=0.02) or MMP-7 (p=0.69). Concentrations of MMPs -7, -8 and -9 correlated with the leukocyte count but not with C-reactive protein (CRP) or neurone-specific enolase (NSE) levels. CONCLUSION: We demonstrated that the systemic levels of MMP-7, -8 and -9 but not TIMP-1 are elevated in cardiac arrest patients in the 48 h post-resuscitation period relative to the healthy controls. Patients who received therapeutic hypothermia had lower MMP-9 levels compared to non-hypothermia treated patients, which generates hypothesis about attenuation of inflammatory response by hypothermia treatment.

A nationwide study of Campylobacter jejuni and Campylobacter coli bacteremia in Finland over a 10-year period, 1998-2007, with special reference to clinical characteristics and antimicrobial susceptibility.

BACKGROUND: Campylobacter bacteremia is an uncommon condition, usually diagnosed in elderly and immunocompromised patients. METHODS: Blood culture isolates and clinical information were collected for patients with diagnoses of Campylobacter jejuni or Campylobacter coli bacteremia in Finland from 1998 through 2007. Bacterial species were identified by means of polymerase chain reaction analysis, and minimal inhibitory concentrations for ciprofloxacin, clindamycin, doxycycline, erythromycin, gentamicin, meropenem, and metronidazole were determined with an agar dilution method. Medical records and mortality data within 1 year after the bacteremic episode were reviewed. RESULTS: The study included 76 patients (median age, 46 years), for whom bacterial isolates (C. jejuni in 73, C. coli in 3) and clinical information were available. Most patients (70%) had no significant underlying diseases. The majority (82%) of the isolates were susceptible for all antimicrobial agents tested. However, antimicrobial therapy seemed to have only a limited effect, because no differences could be detected between patients with appropriate empirical antimicrobial treatment and those with delayed appropriate, inappropriate, or no antimicrobial therapy, either in the duration of hospitalization (median, 4 days for both groups) or in attributable mortality. The outcome of the infection was severe in 4 patients infected with C. jejuni; 2 died within 30 days, spondylodiscitis developed in 1, and Guillain-Barré syndrome developed in 1. CONCLUSIONS: C. jejuni and C. coli bacteremia occurred mainly in moderately young individuals without severe underlying diseases. The bacterial isolates were predominantly susceptible to antimicrobial agents, and the outcome of the disease was typically good, regardless of appropriate or inappropriate antimicrobial treatment given in the hospital.

Serum MMP-8, -9 and TIMP-1 in sepsis: high serum levels of MMP-8 and TIMP-1 are associated with fatal outcome in a multicentre, prospective cohort study. Hypothetical impact of tetracyclines.

Recent evidence suggests that matrix metalloproteinases (MMPs) and their endogenous inhibitors are involved in the pathogenesis of sepsis. We studied serum levels of MMP-8, MMP-9 and TIMP-1 (tissue inhibitor of matrix metalloproteinase-1) in a multicentre, prospective cohort study of patients with sepsis treated in Intensive Care Units (ICUs). We analyzed serum samples taken on ICU admission from 248 critically ill sepsis patients. MMP-8, -9 and TIMP-1 serum levels were analyzed by enzyme-linked immunosorbent assays. Serum MMP-8, MMP-9 and TIMP-1 levels were significantly higher in patients with severe sepsis than in healthy controls. Serum MMP-8 levels among non-survivors (n=33) were significantly (p=0.006) higher than among survivors (n=215). Serum TIMP-1 but not MMP-9 levels were significantly higher among non-survivors than survivors (p<0.0001, p=0.079, respectively). Systemic MMP-8 is upregulated in sepsis suggesting that MMP-8 may contribute to the host response during sepsis. High serum MMP-8 and TIMP-1 levels at ICU admission were seen among patients with fatal outcome. With this background, clinical studies examining the ability of MMP-inhibitors (such as the non-antimicrobial properties of tetracyclines) to diminish the MMP-mediated inflammatory response are needed to develop novel therapies in order to improve the outcome of sepsis.

Is dental treatment of an infected tooth a risk factor for locally invasive spread of infection?

PURPOSE: To determine the impact of antecedent dental procedures and dental health on the course of odontogenic maxillofacial infections requiring hospital care. PATIENTS AND METHODS: In this retrospective cohort study in a referral center, we evaluated medical records and panoramic radiographs of all patients admitted because of odontogenic maxillofacial infection (n = 84). The predictor variables were preceding dental treatment, antimicrobial therapy, and dental health. The outcome variables comprised infection parameters, length of stay, need for intensive care, and management during hospitalization. RESULTS: The mean age of the patients was 43.2 ± 16.5 years and 60% were men. Dental procedure preceded the spread of the infection in 49 cases (58%): endodontic treatment (n = 22), tooth extraction (n = 19), and minor first aid (n = 8). Twenty-seven patients had not received any dental or antimicrobial treatment in the recent past. Antimicrobial treatment alone had been given to 8 patients. Patients without preceding treatment had the highest C-reactive protein levels on admission and at maximum (P = .020 and P = .011) and the highest white blood cell counts on admission (P = .011). Their length of stay was also longer, and they needed intensive care more often than the other patients. Maximum C-reactive protein levels and white blood cell counts between treatment groups did not significantly differ from each other. CONCLUSIONS: The systemic response to the infection was strongest and the course of the infection most severe in the absence of preceding dental treatment and in patients with poor dental health. All types of dental treatment contributed to a less severe course of infection.

Collagenase-2 (MMP-8) as a point-of-care biomarker in periodontitis and cardiovascular diseases. Therapeutic response to non-antimicrobial properties of tetracyclines.

Neutrophil collagenase or collagenase-2 (matrix metalloproteinase [MMP]-8) belongs to the collagenase subgroup of the MMP superfamily of calcium- and zinc-dependent neutral proteinases. MMP-8 is catalytically the most competent proteinase to initiate type I collagen and extracellular matrix degradation associated with periodontal and peri-implant tissue destruction leading to tooth and dental implant loss. Regarding cardiovascular diseases, pathologically excessive MMP-8 has been implicated in atherosclerotic plaque destabilization and rupture probably through its proteolytic ability to thin the protecting collagenous fibrous cap lining coronary and other arteries. During the initiation and course of inflammatory responses in periodontitis, peri-implantitis and cardiovascular diseases, proinflammatory mediators including especially MMP-8 are up-regulated not only in affected tissues but also in the secreted, disease-affected, oral fluids (gingival crevicular fluid [GCF], peri-implant sulcular fluid [PISF], mouthrinse and saliva) as well as in serum and plasma. Regarding periodontitis, peri-implantitis and cardiovascular diseases, the oral fluid and serum MMP-8 analysis has proven to be a sensitive and an objective biomarker as an indicator of health, pathologic processes and pharmacologic response to therapeutic intervention including doxycycline medication as an MMP inhibitor. Oral fluids, i.e., GCF, PISF, mouthrinse and saliva are easily and non-invasively collected for the site- and patient-specific diagnostic analysis in periodontitis and peri-implantitis, whereas serum and/or plasma sample collection is required for diagnosis and monitoring of cardiovascular diseases. Research in periodontology and cardiology has identified a need for the development of innovative point-of-care diagnostic tests for MMP-8. We summarize and review the recent studies on these topics.

Assessment of systemic matrix metalloproteinase and their regulator response in children with Helicobacter pylori gastritis.

BACKGROUND: Helicobacter pylori causes gastritis and is the most important risk factor of peptic ulcer disease and gastric cancer. In chronic adulthood H. pylori infection some matrix metalloproteinases (MMPs), which are proteolytic metalloendopeptidases regulated by tissue inhibitors of metalloproteinases (TIMPs), are upregulated. Our aim was to determine circulating levels of MMPs and their regulators TIMP-1, human neutrophil elastase (HNE) and myeloperoxidase (MPO) in childhood H. pylori infection. DESIGN AND METHODS: Twenty-six H. pylori positive and 34 H. pylori negative children whose H. pylori status was verified by histological examination of gastric biopsies were included. Serum samples were analysed by enzyme-linked immunosorbent assay. RESULTS: Significantly decreased serum levels of TIMP-1 were detected in H. pylori-infected children (median, 97.50 ng/mL) as compared to H. pylori-negative children (median, 118.5 ng/mL, p = 0.003). However, there were no significant differences in serum levels of MMP-2, -7, -8, -9, and their regulators HNE and MPO between H. pylori-positive and -negative children. CONCLUSIONS: Differing from the recent findings in adulthood H. pylori infection, only circulating TIMP-1 levels were significantly different between H. pylori-positive and -negative children. Whether this reflects the first sign of a proteolytic cascade later leading to increased levels of MMPs remains to be shown.

[Rabies]. / Vesikauhu.

Rabies is a mammalian zoonosis caused by a virus belonging to the family of rhabdoviruses. In Finland, the risk of rabies is associated with imported animals and traveling. We describe the second case of human rabies diagnosed in Finland. Strong hydrophobia was present in the initial phase of the disease. The patient had encephalomyelitis, and he died 11 days after the onset of symptoms. Diagnosis was confirmed by RT-PCR using Saliva. Rabies infection leads invariably to death, but can. be prevented after the exposure with vaccine and immunoglobulin therapy.