Matti Nuutinen

Randomised trial of cranberry-lingonberry juice and Lactobacillus GG drink for the prevention of urinary tract infections in women

Abstract Objective: To determine whether recurrences of urinary tract infection can be prevented with cranberry-lingonberry juice or with Lactobacillus GG drink. Design: Open, randomised controlled 12 month follow up trial. Setting: Health centres for university students and staff of university hospital. Participants: 150 women with urinary tract infection caused by Escherichia coli randomly allocated into three groups. Interventions: 50 ml of cranberry-lingonberry juice concentrate daily for six months or 100 ml of lactobacillus drink five days a week for one year, or no intervention. Main outcome measure: First recurrence of symptomatic urinary tract infection, defined as bacterial growth ≥105 colony forming units/ml in a clean voided midstream urine specimen. Results: The cumulative rate of first recurrence of urinary tract infection during the 12 month follow up differed significantly between the groups (P=0.048). At six months, eight (16%) women in the cranberry group, 19 (39%) in the lactobacillus group, and 18 (36%) in the control group had had at least one recurrence. This is a 20% reduction in absolute risk in the cranberry group compared with the control group (95% confidence interval 3% to 36%, P=0.023, number needed to treat=5, 95% confidence interval 3 to 34). Conclusion: Regular drinking of cranberry juice but not lactobacillus seems to reduce the recurrence of urinary tract infection. What is already known on this topic Up to 60% of women will have a urinary tract infection and a third of them will have several recurrences Vaccinium berries and products containing lactobacilli may affect the coliform bacteria that cause urinary tract infection What this study adds 50 ml of cranberry-lingonberry juice concentrate daily reduced recurrences of symptomatic urinary tract infection by about half compared with the control group Lactobacillus GG drink had no effect on recurrence Self treatment with cranberry juice may reduce the need for antimicrobials for recurrent urinary tract infection

Prenatal and Postnatal Factors in Predicting Later Blood Pressure among Children: Cardiovascular Risk in Young Finns

A negative correlation between birth weight and subsequent blood pressure has been reported, but in some studies this correlation has not been found. We analyzed the effect of birth weight and pubertal development and several pre- and postnatal factors on subsequent blood pressure among 2500 children and adolescents in a follow-up study with three surveys conducted with 3-y intervals. The correlations between birth weight and systolic blood pressure varied from -0.04 to 0.02 among the female subjects and from -0.05 to -0.04 among the male subjects in each survey. A somewhat stronger relation was found among the postpubertal female and male subjects (correlation coefficient -0.09 and -0.05) in the last survey. When adjusted for weight, the correlations became negative and more often significant. The decrease in the adjusted mean systolic blood pressure was about 2 mm Hg when birth weight increased from the lowest to the highest tertile. Other factors affecting systolic blood pressure were current age (mean change up to 1.8 mm Hg/y) and weight (mean change up to 1.2 mm Hg/kg), the duration of breast feeding over 3 mo (mean change up to-6.5 mm Hg), and a birth rank order over four (mean change up to 5.0 mm Hg) presented as the mean difference from the baseline. According to the multiple regression analysis, a history of mothers high blood pressure during pregnancy (p < 0.05) predicted future blood pressure more eminently than birth weight. In conclusion, our results based on healthy children and adolescents offer support for the theory of low birth weight as a predicting factor for future blood pressure. However, other pre- and postnatal factors seem to be important as well.

Insulin and blood pressure among healthy children: Cardiovascular risk in young finns☆

We evaluated the role of insulin in regulating and predicting blood pressure among 3596 to 2799 Finnish children and adolescents aged 3 to 18 years who were followed from 1980 to 1986. Blood pressure, weight, and height were measured in three surveys 3 years apart. Fasting blood samples were drawn and serum insulin was analyzed. The effect of insulin on blood pressure was evaluated in each of the 3 study years, together with the effect of fasting insulin on future blood pressure and the effect of insulin on the change in blood pressure. We also analyzed the correlation between insulin and blood pressure in different age groups and the correlation between change in insulin and change in blood pressure. A constant positive correlation was found between insulin and both systolic and diastolic (Korotkoffs fifth phase) blood pressures measured in the respective years (correlation coefficients 0.10 to 0.41 and partial correlation coefficients 0.02 to 0.15), except between insulin and diastolic blood pressure in the first two surveys in terms of partial correlation and multiple regression analysis. Similarly insulin and blood pressure correlated positively in every age group. Insulin measured in 1980 or 1983 predicted systolic blood pressure as measured 3 and 6 years later (correlation coefficients 0.30 to 0.47 and partial correlation coefficients 0.06 to 0.13), and likewise diastolic blood pressure as measured 3 and 6 years later (correlation coefficients 0.17 to 0.35 and partial correlation coefficients 0.05 to 0.08), except among the males in 1983. Correlation between insulin and the change in blood pressure was not significant or remained marginal. Similarly, the correlation between change in insulin and change in blood pressure was not significant or remained marginal. We suggest that insulin seems to regulate actual blood pressure within the normal range and to predict future blood pressure among children and adolescents, independently of age and weight. However, insulin does not enhance the rise in blood pressure.

Recurrence and follow-up after urinary tract infection under the age of 1 year.

Abstract In order to analyze the risk factors for recurrence and the value of routine follow-up by monthly urine cultures in a group of children who had their first episode of urinary tract infection (UTI) under 1 year of age, we performed a retrospective survey of 262 children (134 girls, 128 boys) who were treated for their first UTI while aged under 1 year in the Department of Pediatrics, University of Oulu, during the years 1978–1984. Detailed data on these children concerning their first and recurrent UTIs were collected from hospital records using a formulated data sheet. Causative bacteria and vesicoureteral reflux (VUR) were analyzed as possible risk factors for recurrent UTI. The time of recurrence and the possible symptoms during the recurrent UTI were also investigated. The follow-up period after the first UTI was 3 years; 35% of the boys and 32% of the girls contracted a recurrent UTI during the 3-year follow-up. In 86% of cases, the first UTI recurrence occurred within 6 months of the primary UTI. Recurrent UTIs were detected significantly earlier with routine monthly follow-up compared with those seeking treatment because of symptoms (log rank test P<0.01). There was a significant difference in the number of recurrences of UTI according to the grade of VUR (P=0.006). Recurrence-free survival was shorter and recurrent UTIs occurred more often in the children with grade 3–5 VUR than in those with grade 0–2 VUR (log rank test P=0.0005). Children without VUR and children with grade 1–2 VUR did not differ in the recurrence rate, and thus grade 1–2 VUR did not increase the risk for recurrent UTI. Monthly routine urine cultures are efficient in detecting recurrent UTI infections in children. Since grade 3–5 VUR is a risk factor both for increased recurrence rate of UTI and for possible subsequent renal damage, these children should be followed with monthly urine cultures for UTI recurrences if not on preventive medication. Since the vast majority of UTI recurrences occur within 6 months of the first UTI, routine follow-up for 6 months seems to be sufficient after symptomatic UTI in children with grade 3–5 VUR.

Prevalence, segregation, and phenotype of the mitochondrial DNA 3243A>G mutation in children

We studied the prevalence, segregation, and phenotype of the mitochondrial DNA 3243A>G mutation in children in a defined population in Northern Ostrobothnia, Finland.

Renal manifestations of Henoch–Schönlein purpura in a 6-month prospective study of 223 children

Objective To assess the risk factors for developing Henoch–Schönlein purpura nephritis (HSN) and to determine the time period when renal involvement is unlikely after the initial disease onset. Design A prospective study of 223 paediatric patients to examine renal manifestations of Henoch–Schönlein purpura (HSP). The patients condition was monitored with five outpatient visits to the research centre and urine dipstick testing at home. Results HSN occurred in 102/223 (46%) patients, consisting of isolated haematuria in 14%, isolated proteinuria in 9%, both haematuria and proteinuria in 56%, nephrotic-range proteinuria in 20% and nephrotic-nephritic syndrome in 1%. The patients who developed HSN were significantly older than those who did not (8.2±3.8 vs 6.2±3.0 years, p<0.001, CI for the difference 1.1 to 2.9). Nephritis occurred a mean of 14 days after HSP diagnosis, and within 1 month in the majority of cases. The risk of developing HSN after 2 months was 2%. Prednisone prophylaxis did not affect the timing of the appearance of nephritis. The risk factors for developing nephritis were age over 8 years at onset (OR 2.7, p=0.002, CI 1.4 to 5.1), abdominal pain (OR 2.1, p=0.017, CI 1.1 to 3.7) and recurrence of HSP disease (OR 3.1, p=0.002, CI 1.5 to 6.3). Patients with two or three risk factors developed nephritis in 63% and 87% of cases, respectively. Laboratory tests or blood pressure measurement at onset did not predict the occurrence of nephritis. Conclusion The authors recommend weekly home urine dipstick analyses for the first 2 months for patients with HSP. Patients with nephritis should be followed up for more than 6 months as well as the patients with HSP recurrence.

Childhood Encephalopathies and Myopathies: A Prospective Study in a Defined Population to Assess the Frequency of Mitochondrial Disorders

Objectives. To assess the frequency of mitochondrial abnormalities in muscle histology, defects in respiratory chain enzyme activities, and mutations in mitochondrial DNA (mtDNA) in children with unexplained psychomotor retardation in the population of Northern Finland. Background. The frequency of mitochondrial diseases among patients with childhood encephalopathies and myopathies is not known. Frequencies are difficult to estimate because the clinical presentation of these disorders is variable. Methods. A total of 116 consecutive patients with undefined encephalopathies and myopathies were enrolled during a 7-year period in a hospital serving as the only neurologic unit for a pediatric population of 97 609 and as the only tertiary level neurologic unit for a pediatric population of 48 873. Biochemical and morphologic investigations were performed on muscle biopsy material, including oximetric and spectrophotometric analyses of oxidative phosphorylation, histochemistry, electron microscopy, and molecular analysis of mtDNA. Results. Ultrastructural changes in the mitochondria were the most common finding in the muscle biopsies (71%). Ragged-red fibers were found in 4 cases. An oxidative phosphorylation defect was found in 26 children (28%), complex I (n = 15) and complex IV (n = 13) defects being the most common. Fifteen percent of patients (n = 17/116) with unexplained encephalomyopathy or myopathy had a probable mitochondrial disease. Common pathogenic mutations were found in the mtDNA of only 1 patient (.9%). Conclusions. The common known mutations in mtDNA are rarely causes of childhood encephalomyopathies, which is in contrast to the considerable frequency of the common MELAS mutation observed among adults in the same geographical area. Biochemically and morphologically verified mitochondrial disorders were nevertheless common among the children, making the analysis of a muscle biopsy very important for clinical diagnostic purposes.

Consequences of caustic ingestions in children

A retrospective analysis of 98 patients, less than 15 years of age, treated for caustic ingestion during 1976–1990 was performed to evaluate the modern consequences of caustic ingestion in children and to set indications for esophagoscopies and radiographic and laboratory examinations. Dishwasher detergents were ingested by 56 children. There were no lye ingestions, since lye has not been freely available in Finland since 1969. Household acetic acid (vinegar) was the most commonly (12/23) ingested acid. Primary esophagoscopy was performed in 79 of the 98 cases (80.6%). Esophageal burns were found in 20 patients. Acids caused burns more often than alkalies (9/23 (39.1%) versus 11/75 (14.7%); p = 0.011; 95% confidence intervals (CI) for the difference 5.6–43.3%) and acid burns more often developed into scars (7.4% versus 4%; p = 0.029; 95% CI for the difference 1.4–25.4%). The only esophageal stricture developed after ingestion of a Clinitest tablet. The mean time for hospitalization as a result of acid ingestion was significantly longer than after alkaline ingestion (3.2 (SD 3.5) days, n = 23 versus 1.5 (1.6) days, n = 15; p < 0.05; 95% CI for the difference 0.7–2.8 days). Prolonged drooling and dysphagia (12–24h) predicted esophageal scar formation with 100% sensitivity and 90.1% specificity, but signs and symptoms did not predict esophageal burns after primary esophagoscopy. Radiographic examinations and leukocyte counts were of no value in predicting esophageal burns and scars. The panorama of caustic ingestion appears to have changed, probably due in part to the law banning sale of lye products since 1969. This type of law should be encouraged elsewhere. Acids cause even more caustic burns than alkalies. Vinegar should be regarded as a potent caustic substance and distributed in baby‐safe bottles with appropriate information on its caustic nature. As severe esophageal lesions after accidental ingestion of caustic substances are now rare in children, primary esophagoscopies and hospitalization of patients are not indicated routinely. The decision on esophagoscopy can be made on the basis of drooling and dysphagia during follow‐up.

Clinical course of extrarenal symptoms in Henoch–Schönlein purpura: a 6-month prospective study

Objective To describe the extrarenal symptoms and clinical course of Henoch–Schönlein purpura (HSP). Design A prospective national multicentre trial with 6-month follow-up. Patients A total of 223 newly diagnosed paediatric HSP patients. Results Purpura was the initial symptom in 73% of the patients and was preceded by joint or gastrointestinal manifestations in the rest by a mean of 4 days. Joint symptoms, abdominal pain, melena, nephritis and recurrences occurred in 90%, 57%, 8%, 46% and 25% of the patients, respectively. Orchitis affected 17/122 (14%) of the boys. Seven patients developed protein-losing enteropathy characterised by abdominal pain, oedema and serum albumin under 30 g/l, and an additional 49 patients had subnormal albumin levels without any proteinuria. Positive fecal occult blood (26/117, 22%) and α1-antitrypsin (7/77, 9%) suggested mucosal injury even in the patients without gastrointestinal symptoms. HSP was often preceded by various bacterial, especially streptococcal (36%) and viral infections. Previous streptococcal infection did not induce changes in the level of complement component C3. Recurrences were more frequent in patients >8 years of age (OR 3.7, CI 2.0 to 7.0, p<0.001) and in patients with nephritis (OR 4.6, CI 2.3 to 8.9, p<0.001). Patients with severe HSP nephritis had more extrarenal symptoms up to 6 months. There was no difference in the clinical course between the prednisone-treated and non-treated patients during the 6-month follow-up. Conclusions Serum albumin is often low in HSP patients without proteinuria, due to protein loss via the intestine. Although corticosteroids alleviate the symptoms, they seem not to alter the clinical course of HSP during 6 months of follow-up.

Adverse reactions in children during long term antimicrobial therapy

BACKGROUND It is difficult to obtain reliable date on the rate of adverse reactions caused by drugs in general use. Yet it would be important to compile data on adverse reactions to long-term antimicrobial therapy. METHODS A sample of 1607 girls and 218 boys from 16 409 children younger than 16 years who had received long term antimicrobial therapy for recurrent urinary tract infections during 1976 to 1985 was analyzed with regard to adverse reactions. RESULTS Altogether 5066 courses of treatment were given to female patients and 607 to male patients. Adverse reactions were reported in 589 courses of the 5673 (10.4%), and 463 courses (8.2%) were discontinued because of adverse reactions. None of the patients had serious life-threatening reactions, and none of those receiving nitrofurantoin had pulmonary problems. The most common adverse reactions associated with the use of nitrofurantoin were nausea and vomiting (rate, 4.4/100 person years at risk; 95% confidence interval, 3.4 to 5.4), whereas sulfonamides caused most commonly allergic skin reactions (rate, 4.6; 95% confidence interval, 3.2 to 6.5). Patients younger than the age of 2 years receiving nitrofurantoin had adverse reactions more often than those who received sulfonamides, but in the age group 2 to 15 years sulfonamides caused adverse reactions leading to discontinuation of treatment more often than did nitrofurantoin of treatment the adverse reactions occurred during the first 6 months of treatment. CONCLUSIONS We found nitrofurantoin and sulfonamides to be safe drugs for use in long term preventive antimicrobial therapy.