Tonsillar microbiota in children with PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and adenitis) syndrome.

Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) is a childhood febrile syndrome of unknown origin that is often cured with tonsillectomy. We aimed to compare the bacterial microbiota of the tonsils removed from PFAPA patients with those of controls. We used next-generation sequencing technology to investigate the bacterial microbiota of the tonsils of 30 PFAPA patients and 24 controls. We found significant differences in the presence and relative abundance of many bacteria between PFAPA cases and controls. For example, cyanobacteria, potential producers of microcystins and other toxins, were more common in the case samples (14/30, 47 %) than in the controls (4/24, 17 %, p = 0.02), and the mean relative abundance of cyanobacteria was higher in the case samples (0.2 %) than in the controls (0.01 %, p = 0.01). Streptococci were present in all samples in both groups, but their mean relative abundance was lower in the case samples (3.7 %) than in the controls (9.6 %, p = 0.01). Typical nasopharyngeal microbes such as fusobacteria, Prevotella, Tannerella, Porphyromonas, and Parvimonas dominated the microbiota of the tonsils in both groups. The microbiota of the tonsils removed from PFAPA patients differed significantly from those of the controls. Tonsillar microbiota may play a role in triggering the inflammatory processes that lead to symptoms of PFAPA.

Escherichia coli biofilm formation and recurrences of urinary tract infections in children.

It has been suggested that biofilm formation by uropathogenic Escherichia coli (UPEC) isolates is associated with recurrence and persistence of urinary tract infection (UTI). We compared the in vitro biofilm formation of UPEC isolates from children with acute or recurrent UTI. Employing 206 consecutive clinical UPEC isolates from children with proven UTI, i.e., pyelonephritis (n = 78), recurrent pyelonephritis (n = 10), cystitis (n = 84) or recurrent cystitis (n = 34), we applied 1 % crystal violet staining to polystyrene microtitre plates at 72 h and measured the optical density (OD) values. The method had been validated to measure biofilm formation against confocal laser scanning microscopy and scanning electron microscopy. The OD values were lower in the recurrent cystitis group than in the other groups (mean OD 0.36, SD 0.21 vs mean 0.47, SD 0.36, P = 0.04) and higher in the recurrent pyelonephritis group than in the other groups (mean OD 0.69, SD 0.33 vs mean OD 0.44, SD 0.34, P = 0.006) indicating biofilm formation of strains causing recurrent pyelonephritis. It appears that the properties of UPEC isolates required for effective biofilm growth on an abiotic surface are important for recurrent pyelonephritis, but not for recurrent cystitis. It would be valuable in the future to analyze whether the biofilm properties of E. coli observed in vitro predict a slower clinical response to antimicrobial treatment and increased renal scar formation after UTI.

Initial oxygen saturation values can predict the need to hospitalise children with mild wheezing.

AIM: Mild wheezing during respiratory infections is a common cause of paediatric hospital admissions. This study aimed to identify factors predicting this condition in children over six months of age. METHODS: We reviewed the medical records of 539 children, aged 6 months to 16 years, who visited the emergency department because of wheezing during respiratory infection. Mild disease was defined as hospital stays of less than 48 h and severe disease was staying at least 48 h or being treated in intensive care. Patients with an initial oxygen saturation value (SaO2 ) below 90% were analysed separately. RESULTS: Most (87%) of the 539 patients had mild disease, 6% had a severe disease and 7% had an initial SaO2 below 90%. The area under the receiver operating characteristic (ROC) curve for the initial SaO2 predicting mild disease was 0.75 (95% CI 0.53-0.97), and the optimal cut-off value was 93%. An initial SaO2 >93% had a negative predictive value of 93%. Although 270 patients (50%) were hospitalised, only 140 (26%) would have been admitted using an optimal cut-off of SaO2 ≤93%. CONCLUSION: An initial SaO2 >93% reflects a mild course of acute wheezing and using this cut-off point could have almost halved hospital admissions.

Infants under 6 months with bronchiolitis are most likely to need major medical interventions in the 5 days after onset.

AIM: This study examined the need for, and timing of, major medical interventions (MMIs) in infants under 6 months of age with bronchiolitis. METHODS: We reviewed the medical records of 353 children who visited our emergency department with bronchiolitis. MMI was defined as the need for any of the following interventions during admission: supplementary oxygen, intravenous fluids, intravenous antibiotics or admission to the intensive care unit. RESULTS: Altogether 19% of the 353 patients required a MMI and 3% had apnoea. The patients with apnoea were all under 2 months of age, and 90% had a respiratory syncytial virus (RSV) infection and 40% had been born prematurely. The risk of needing a MMI continued for up to 5 days after disease onset. A positive RSV test predicted a MMI with an odds ratio (OR) of 11.5 (95% CI 2.6-50.5), and a fever of over 38°C predicted a MMI with an OR of 3.5 (95% CI 1.4-8.8). Each 1% increase in the initial oxygen saturation value was associated with a decreased risk of MMI (OR 0.7, 95% CI 0.6-0.8). CONCLUSION: Infants under 6 months of age with bronchiolitis were most likely to need MMIs in the first 5 days after disease onset.

Biofilm formation and virulence of uropathogenic Escherichia coli in urine after consumption of cranberry-lingonberry juice.

Cranberry-lingonberry juice (CLJ) was effective in preventing urinary tract infections (UTIs) in our earlier randomized clinical trial. We aimed to test whether consumption of CLJ at a similar dose to earlier reduces the biofilm formation and virulence of uropathogenic Escherichia coli in urine. Twenty healthy women drank 100 ml of CLJ daily for two weeks. Urine samples were obtained 2-4 hours after the last dose. Control samples were taken after a one-week period without berry consumption. Biofilm formation of 20 E. coli strains was measured at 72 hours by the polystyrene microtitre plate method. Quantitative real-time PCR analyses were performed for selected genes. Four of the 20 clinical strains produced more biofilm in urine after CLJ consumption (P < 0.05) and one produced less. Expression levels of the pga, cpxA, fimA and papF genes did not differ between bacteria grown in control urine and urine obtained after CLJ consumption, except for pga gene expression, which was reduced in one strain after CLJ (P = 0.04). It appears that the effect of CLJ in preventing UTIs is not explained by mechanisms that reduce biofilm formation or the expression of selected virulence genes of Escherichia coli in urine.

Mutations in the tyrosine phosphatase CD45 gene in a child with severe combined immunodeficiency disease.

The hematopoietic-specific transmembrane protein tyrosine phosphatase CD45 functions to regulate Src kinases required for T- and B-cell antigen receptor signal transduction. So far, there have been no reports to our knowledge of a human deficiency in a tyrosine-specific phosphatase. Here, we identified a male patient with a deficiency in CD45 due to a large deletion at one allele and a point mutation at the other. The point mutation resulted in the alteration of intervening sequence 13 donor splice site. The patient presented at 2 months of age with severe combined immunodeficiency disease. The population of peripheral blood T lymphocytes was greatly diminished and unresponsive to mitogen stimulation. Despite normal B-lymphocyte numbers, serum immunoglobulin levels decreased with age. Thus, CD45 deficiency in humans results in T- and B-lymphocyte dysfunction.

Cardiac troponin-I as a screening tool for myocarditis in children hospitalized for viral infection.

AIM: The incidence of myocarditis in children is uncertain because patients with minor symptoms can remain undiagnosed. We hypothesized that screening all children who are hospitalized for an acute infection with troponin-I (TnI) would reveal myocarditis cases and performed a prospective screening study. METHODS: Between October 2005 and July 2008, a blood sample for TnI measurement was taken every time a sample for C-reactive protein measurement was drawn. If TnI value was above the screening limit (0.06 microg/L), electrocardiogram (ECG) and cardiac ultrasound were performed. TnI measurements were repeated until at normal level. RESULTS: Altogether, 1009 children were screened during the 33 months. TnI was above the screening limit (0.06 microg/L) in six children. None of them had any signs of myocarditis in ECG or cardiac ultrasound. Five of those six children were younger than 30 days. All had a respiratory infection as a cause for hospitalization, three of which was caused by RSV. In four children, all younger than 30 days, TnI levels remained high (>0.37 microg/L) for two months, but decreased after that to normal levels. CONCLUSION: The incidence of myocarditis during viral infections is low and a routine TnI screening for asymptomatic myocarditis is not useful.

Occurrence of vesicoureteral reflux in children.

AIM: The reported low occurrence of vesicoureteral reflux in the general population seems implausible. We wanted to test the hypothesis that reflux is more common and more independent of urinary-tract infection than has previously been thought. METHODS: We tested our hypothesis by analysing the characteristics of 406 consecutive children aged <5years who had been referred for consultation because of urinary-tract infection. Using data on their urine samples, we evaluated the reliability of the urinary-tract infection diagnosis and analysed the frequencies of vesicoureteral reflux and abnormal ultrasound findings in three reliability groups (A: certain urinary-tract infection, B: possible and C: improbable). RESULTS: The occurrence of reflux was the same irrespective of the diagnostic reliability of urinary-tract infection (A: 98/276 [36%] versus B: 13/46 [28%] versus C: 9/25 [36%]). Most of the abnormal ultrasound findings (58/71, 80%) were found among patients with a certain diagnosis (Group A). CONCLUSION: We suggest that vesicoureteral reflux is more common in children even without urinary-tract infection than has been thought previously. The guidelines recommending a search for reflux by means of voiding cystourethrography should be reconsidered.

Impact of multiplex respiratory virus testing on antimicrobial consumption in adults in acute care: a randomized clinical trial.

OBJECTIVES: Inappropriate use of antibiotics is associated with development of antimicrobial resistance. In respiratory infections it is often difficult to differentiate between viral and bacterial infections, and empirical treatment is common. Enhanced viral testing is expected to clarify clinical decision-making and reduce the prescription of antibacterial agents, but the impact of such information on patient care is unclear. METHODS: We conducted a (1:1) randomized controlled clinical trial involving 998 adults with respiratory symptoms, fever, chest pain or poor general condition in the emergency unit of a tertiary hospital. Multiplex PCR results for 496 patients were available in 24 hours (intervention group) and those for the remaining 502 patients were available in 7 days (control group). Our primary outcome measures were the duration of hospitalization and the consumption of antibiotics within 30 days of enrolment. RESULTS: In all, 841 of 998 (84%) patients had respiratory symptoms at study entry. A respiratory virus was detected in 175 (17.5%). The mean duration of hospitalization was 4.2 days (SD 5.4) in the intervention group and 4.1 days (SD 4.9) in the control group (difference 0.1, 95% CI -0.5 to 0.6, p 0.810). The mean days on antibiotics were 11.3 days (SD 12.6) in the intervention group and 10.4 days (SD 11.4) in the control group (difference 0.9, 95% CI -0.6 to 2.4, p 0.235). CONCLUSIONS: Multiplex PCR testing for respiratory viruses with results available within 24 hours did not reduce the consumption of bacterial antibiotics or the length of hospital stay in adults presenting with respiratory symptoms, fever, chest pain or reduced general condition in acute care.

Biofilm formation by Escherichia coli isolated from patients with urinary tract infections.

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.

Hospital-associated infections during and after care in a paediatric infectious disease ward.

Viruses are important causes of paediatric hospital-associated infections (HAIs). We evaluated the frequency of viral HAIs during hospitalisation and after discharge in a paediatric infection ward. Data were collected prospectively for two years with follow-up questionnaires in which parents reported symptoms of new infections. Infections occurring >72 h after admission to hospital or <72 h after discharge were regarded as hospital-associated. The mean age of patients was 3.0 years and the mean hospitalisation time 3.0 days. Twenty-one out of the 1927 patients [1.1%, 95% confidence interval (CI): 0.7-1.7] developed an HAI during hospitalisation, in every case diarrhoea. A total of 1175 (61%) questionnaires were returned. In all, 86 children (7.3%, 95% CI: 5.9-9.0) had new symptoms within 72 h of discharge, most often diarrhoea (49%). Older age protected against HAI [odds ratio (OR, per year in age): 0.92; 95% CI: 0.85-0.99; P=0.02]. Among the patients hospitalised for respiratory infections, a shared room increased the risk of HAI (OR: 2.3; 95% CI: 1.1-4.8; P=0.03). Eight percent of the patients in our ward, where alcohol hand gel is actively used and single rooms are common, developed an HAI. Eighty percent of the HAIs appeared at home, which emphasises the importance of post-discharge follow-up.

A randomized, controlled trial of tonsillectomy in periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome.

OBJECTIVE: We carried out a prospective, randomized, controlled trial to clarify the effect of tonsillectomy on the clinical course of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome. STUDY DESIGN: Twenty-six consecutive children (mean age 4.1 years) with at least 5 PFAPA attacks were recruited from 3 tertiary care pediatric hospitals during 1999-2003 and randomly allocated to tonsillectomy or follow-up alone. They were all followed up with symptom diaries for 12 months. Tonsillectomy was allowed after 6 months in the control group if the attacks recurred. RESULTS: Six months after randomization all 14 children in the tonsillectomy group and 6/12 children in the control group (50%) were free of symptoms (difference 50%, 95% confidence interval 23% to 75%, P < .001). Tonsillectomy was performed on 5/6 of the patients in the control group who still had symptoms after 6 months. The remaining unoperated child in the control group had recurrences of the fever episodes throughout the follow-up, but the symptoms became less severe, and the parents did not choose tonsillectomy. CONCLUSION: Tonsillectomy appeared to be effective for treating PFAPA syndrome. The fever episodes ceased without any intervention in half of the control subjects. We conclude that although the mechanisms behind this syndrome are unknown, tonsillectomy can be offered as an effective intervention for children with PFAPA.

Recurrent acute otitis media detracts from health-related quality of life.

OBJECTIVE: Acute otitis media causes discomfort to children and inconvenience to their parents. This study evaluated the quality of life in children with recurrent acute otitis media aged less than 24 months. METHODS: Quality of life was evaluated in 149 children aged 10 to 24 months who were referred to the Oulu University Hospital on account of recurrent acute otitis media. The children were treated with or without surgery. Age-matched controls were selected randomly from the general child population. Parents completed the Child Health Questionnaire. RESULTS: The children with recurrent acute otitis media had a significantly poorer quality of life than control children. The control children with a history of a few acute otitis media episodes had a significantly poorer quality of life than those without any such history. The quality of life of the children with recurrent acute otitis media improved during the one-year follow up, regardless of the treatment, but did not reach the same level as healthy children. CONCLUSION: Acute otitis media detracted from quality of life when a generic measure was used. The mode of treatment used to prevent further recurrences of acute otitis media did not influence quality of life improvement.

Influence of film digitization on radiological interpretation.

Our objective was to evaluate the influence of changing from analogue to digital imaging on interobserver and intraobserver image interpretation. Three radiologists interpreted 96 three image series of occipitomental radiographs of paranasal sinuses from the films and from the corresponding digitized images from the screen. Images were classified according to degree of abnormality as either normal, with mucosal thickening of less than 5 mm, with mucosal thickening of 5 mm or more, total opacity, air-fluid level or polyp or cyst of maxillary sinuses. In the present study we found that there were more differences between two radiologist's interpretations with a single method than in a single radiologist's interpretations between the methods, although radiologists interpreted fewer pathological findings from the digitized images than from the corresponding films. Our data show that the results of image interpretation are preferentially dependent on the reader rather than on the method of reading.

A review and meta-analysis of hormonal treatment of cryptorchidism.

To assess the effect of LH-releasing hormone (LHRH) and hCG in the treatment of cryptorchidism, 33 articles published in English between 1958-1990 were analyzed. Altogether, 3282 boys with 4524 undescended testes were included in the analysis; 872 boys with 1174 undescended testes were treated in randomized trials. The meta-analysis showed LHRH to be more effective than placebo; the risk ratio was 3.21 [95% confidence interval (CI) of 1.83-5.64] and 2.57 (95% CI, 1.39-4.74) in trials excluding retractile testes, respectively. In the combined randomized trials, the success rate with LHRH was 21% (95% CI, 18-24%), that with hCG was 19% (95% CI, 13-25%), and that with placebo was 4% (95% CI, 2-6%). The effect of the hormonal treatment was overestimated in nonrandomized trials. In conclusion, LHRH is effective in the treatment of cryptorchidism, and hCG is more effective than placebo, but data about the effect are scanty.

Serum fatty acids in 8-year-old Finnish boys: correlations with qualitative dietary data and other serum lipids.

To survey risk factors in coronary heart disease in Finnish children, fasting serum specimens from 244 healthy 8-yr-old boys were analyzed for the fatty acid composition of cholesterol esters (CE), triglycerides (TG), free fatty acids (FFA), and phospholipids (PL). A qualitative dietary survey was made by asking parents to answer a questionnaire including, among others, a question on the kind of fat usually used on bread by the child. The mean percentages of linoleate (18:2) in serum cholesterol esters, triglycerides, free fatty acids, and phospholipids were 53.1, 13.5, 11.5, and 22.7%, respectively, which represent an international average. The quality of dietary fat had a clear influence on serum fatty acids, eg, the content of 18:2 in CE was 56.8 +/- 3.6% in boys using soft vegetable margarine and 50.5 +/- 3.6% in those using butter. The former had also a marginally lower serum total cholesterol (4.87 +/- 0.86 mmol/l) than the latter (5.08 +/- 0.80 mmol/l). Serum total cholesterol showed significant negative correlations with the percentage of 18:2 in all four lipid fractions, the highest r values being with PL-18:2 (-0.41) and CE-18:2 (-0.24). Accordingly, serum cholesterol was lower in the highest CE-18:2 quartile (4.67 +/- 0.76 mmol/l) compared with the lowest (5.30 +/- 0.70 mmol/l; p less than 0.001). The results indicate that when serum fatty acids are used as indicators of the quality of dietary fat, a negative association between polyunsaturated fat and serum cholesterol may be demonstrable even within a free-living population.

Fatty acid composition of serum cholesteryl esters in 3- to 18-year-old Finnish children and its relation to diet.

The composition of fatty acids in serum cholesteryl esters (CE) was analyzed gas chromatographically in 1348 boys and girls aged from 3 to 18 yr. A dietary survey was carried out simultaneously using the 48-h recall method. The dietary P/S ratio had highly significant correlations with CE fatty acids: positive with linoleate (0.567) and total omega 6 fatty acids and negative with saturated, monounsaturated, and omega 3 polyunsaturated fatty acids. The highest mean percentage of CE-linoleate was found in 15-yr-old girls (52.7, SD 4.68%) and lowest in 3-yr-old girls (48.1, SD 5.00%). Age, sex, and the degree of puberty had no independent effect on CE-linoleate after it had been adjusted for the effect of dietary P/S ratio by analysis of covariance. These results indicate that the fatty acid composition of serum CE depends on the quality of dietary fat and that CE-linoleate is a useful reflector of the dietary P/S ratio. The negative correlation between CE omega 3 fatty acids and dietary P/S ratio may be due to displacement of the omega 3 acids in serum CE by the much higher proportion of dietary linoleate.

Three-year tracking of serum fatty acids in Finnish boys and girls.

The composition of fatty acids in serum lipids has been shown to reflect the quality of dietary fat. In order to examine the long-term stability (tracking) of the serum (and hence dietary) fatty acid composition serum cholesteryl ester fatty acids were analysed by gas chromatography in a randomly selected population sample of 1029 Finnish boys and girls aged 3, 6, 9, 12, 15 and 18 years, and again from the same individuals 3 years later. The tracking was evaluated by calculating linear correlation coefficients for the percentages of individual fatty acids between the 2 time points. For all fatty acids the correlations were highly significant, e.g. for linoleate and arachidonate they were 0.58 and 0.61, respectively. In 1980 the means of the percentages of some fatty acids showed certain differences between the various age and sex groups; in 1983 these differences had become smaller and had largely shifted towards three years older age groups, implying that the differences were due to dietary differences between the cohorts rather than to age and sex per se. The present results indicate that serum fatty acid composition has a fairly good biological reproducibility (tracking) and suggest that age and sex as such are only minor determinants of the serum fatty acid composition.

Fatty acid composition of serum cholesteryl esters in relation to serum lipids and apolipoproteins in 3-18-year-old Finnish children and adolescents.

Serum cholesteryl ester (CE) fatty acids, serum lipids and apolipoproteins were analysed from 1348 Finnish children aged from 3 to 18 years. The study was part of a comprehensive survey of coronary heart disease risk factors and their determinants in Finnish children and adolescents. The percentage of CE linoleate (18:2) had significant negative correlations with the serum concentrations of total and LDL cholesterol, triglycerides as well as apo B. The associations of HDL to CE fatty acids were weak, although there was a significant positive correlation of CE-18:2 to HDL cholesterol and apo A-I. The ratio of HDL to total cholesterol and the ratio of apo A-I to apo B increased strongly in quintiles of increasing percentage of CE-18:2. In conclusion, the present results show significant associations between serum CE fatty acid composition and the different components of serum lipoproteins among free-living Finnish children and imply a relation between the quality of dietary fats and serum lipoproteins within this population.

Plasma cholesteryl ester fatty acids in 3- and 12-year-old Finnish children.

Risk factors associated with coronary heart disease were surveyed in a multicentre study carried out in 1979 among children living in different parts of Finland. The survey included analyses of plasma lipids and cholesteryl ester (CE) fatty acids as well as a dietary interview by a 48-hour recall method. The present report gives the plasma fatty acid compositions obtained from 181 3-year-old and 226 12-year-old children and their relations to dietary factors and other plasma lipids. The mean percentages (+/- SD) of CE linoleate in the 3- and 12-year-old children were 49.2 +/- 5.2 and 5.10 +/- 51.0%, respectively. Differences in CE fatty acid composition between the various regions of Finland were relatively small, but there was a trend to higher proportions of polyunsaturated fatty acids in western and urban compared with eastern and rural communities. Among different dietary constituents the daily intake of margarine + oils or butter had the greatest effect on plasma CE fatty acid composition. There was a highly significant positive correlation between the dietary P/S ratio and the percentage of CE linoleate in plasma.