Longitudinal follow-up of bladder function in children who participated in the Swedish Reflux Trial.

BACKGROUND: Several publications have reported the coexistence of vesicoureteral reflux (VUR) and bladder dysfunction in children. Whether this dysfunction remains in the longer term is not yet known. OBJECTIVE: This study revisited children who participated in the Swedish Reflux Trial (SRT) with the primary aim of evaluating whether bladder and bowel dysfunction (BBD) in these patients persisted until adolescence. The secondary aim was to evaluate two BBD subgroups, and relations to recurrent urinary tract infections (UTI). STUDY DESIGN: Of the 161 eligible children at SRT study-end, 73 children participated. Their bladder function was evaluated longitudinally using a validated BBD questionnaire with symptom score (cut-off ≥7) and uroflowmetry, at five (T2) and ten years (T3) after study-end. T1 was the SRT study-end. Besides BBD, the sub-diagnoses overactive bladder (OAB) and dysfunctional voiding symptoms (DVS) were calculated from symptom scores. RESULTS: BBD was diagnosed in 37% of children at mean age 3.7 years, which decreased with age to 23% of adolescents (mean age 15.7). DVS and OAB subgroups were equally common at T1, but only DVS was identified at the last follow-up (T3) (p = 0.0008). Recurrent UTIs were seen in 17% at T3 and were more common in patients with BBD (p = 0.038). The gender distribution of BBD also changed, from being equally common at the end of the SRT to affecting mainly adolescent girls at the last follow-up (p = 0.022). Information was available regarding VUR status after repeat VCUGs during follow-up in 22 patients, 12 of them after endoscopic treatment. An improvement in VUR grade was found in the 22, but during follow-up numbers with BBD or UTI did not differ between treated and non-treated groups. DISCUSSION: The prevalence of BBD decreased from 37% at 3-4 years of age to 23% in adolescence, when it was almost exclusively seen in girls. BBD and the subgroup DVS were associated with UTI. Even if epidemiological studies have established a predisposition to bladder symptoms and UTI in girls, little is known about bladder function in adolescents with a history of VUR during the first years of life. One limitation of the study was the number of patients participating. Also, the number of patients with kidney damage was more common in the cohort. CONCLUSION: In this longitudinal follow-up of BBD in children with VUR, the number of children with BBD decreased with age. In adolescence, both BBD and recurrent UTIs mainly affected girls.

Four-hour voiding observations detect neurogenic lower urinary tract dysfunction in neonates with anorectal malformation.

INTRODUCTION: Neurogenic lower urinary tract dysfunction (LUTD) has been reported in 20-50% of children with anorectal malformations (ARM). As neurogenic LUTD represents an inherent risk of renal deterioration and urinary tract infections, an early diagnosis is important. The gold standard for evaluating neurogenic LUTD involves invasive urodynamic testing but a useful addition should be an easy-to-perform, non-invasive method of screening. OBJECTIVE: In this study, we evaluate non-invasive 4 h voiding observations as a screening method for neurogenic LUTD in ARM children. STUDY DESIGN: Thirty-four patients with ARM, excluding those with perineal fistulas, were evaluated using both 4 h voiding observation and urodynamic testing before and after posterior sagittal anorectoplasty (PSARP) at median ages of 0.3 and 1.1 years. In the urodynamic assessment, the gold standard for neurogenic LUTD, nine children received the diagnosis, eight innate and one post-surgery. RESULTS: Five boys with a high urethral fistula and anomalies of the spinal cord had urodynamically diagnosed neurogenic LUTD, a dysfunction also identified in the 4 h voiding observations. The pattern was characterised both by an increase in the number of voiding and the number of interrupted voiding, urinary leakage and elevated residual urine (Figure). In three girls with a vestibular fistula and tethered cord, an urodynamic investigation identified suspected mild neurogenic LUTD. In the voiding observations, an abnormal voiding pattern was not as obvious in the girls as in the five males. One girl with cloaca showed signs of postsurgical denervation damage, which was easily identified in the 4 h voiding observations (high capacity and elevated residual urine). DISCUSSION: In the present study, gender differences in the severity of dysfunction reflected in the free voiding pattern in infants with ARM and neurogenic LUTD is probably the result of the different underlying causes of neurogenic LUTD in boys and girls. Boys with the condition have a congenital malformation of the caudal part of the spinal cord and girls a tethering of the cord. The most obvious limitation of the study was the low number of patients. Despite this, we consider the results worth reporting, since we found that results in the free voiding observations effectively confirmed what was established in the urodynamic investigations. CONCLUSION: In pre-PSARP patients, 4 h voiding observations can be used to screen for severe neurogenic LUTD requiring attention and treatment. When post-surgical denervation is suspected, the voiding observation is also a good method for indicating the diagnosis.

Development and Validation of Symptom Score for Total Bladder-Bowel Dysfunction: Subscales for Overactive Bladder and Dysfunctional Voiding.

PURPOSE: Bladder-bowel questionnaires are an important tool in diagnosing nonneurogenic bladder-bowel dysfunction in children. We report the validity and reliability of a bladder-bowel questionnaire that has been in clinical use at our institution for decades. MATERIALS AND METHODS: The bladder-bowel questionnaire contains 13 questions, with answers ranging from never (score of 0) to daily (3). The questionnaire was answered by 139 healthy controls and 134 children 3 to 16 years old diagnosed with bladder-bowel dysfunction by a pediatric urologist/urotherapist. A subdiagnosis of overactive bladder or dysfunctional voiding was made in each patient. Bladder-bowel questionnaire scales were developed and evaluated against hypotheses of validity (known groups/convergent/discriminating) and reliability (internal consistency/retest reliability), sensitivity and specificity. Responsiveness was tested in 80 patients who answered the bladder-bowel questionnaire after treatment. RESULTS: A total bladder-bowel dysfunction score scale demonstrated the ability to discriminate between patients with bladder-bowel dysfunction and healthy subjects. It resulted in a ROC curve with AUC of 0.96. The maximized sensitivity was 94% and specificity was 89% for a cutoff score of 7. Two subscales were identified referring to 6 filling phase items and 3 voiding phase items. When tested in patients with overactive bladder and dysfunctional voiding, respectively, multivariable scales performed sufficiently to discriminate between those with and without overactive bladder, and those with and without dysfunctional voiding. All of these scales fulfilled the evaluated requirements for validity and reliability. At 1 year after treatment all scale scores corresponded to patient improvement (p <0.0001), suggesting the bladder-bowel questionnaire can detect clinical change over time. CONCLUSIONS: The bladder-bowel questionnaire is valid and reliable for diagnosing bladder-bowel dysfunction in pediatric patients, and overactive bladder and dysfunctional voiding in those with bladder-bowel dysfunction.

Effectiveness, safety, and acceptability of first-trimester medical termination of pregnancy performed by non-doctor providers: a systematic review.

BACKGROUND: Previous systematic reviews have concluded that medical termination of pregnancy (TOP) performed by non-doctor providers may be as effective and safe as when provided by doctors. Medical treatment of incomplete miscarriage by non-doctor providers and the treated women's acceptance of non-doctor providers of TOP has not previously been reviewed. OBJECTIVES: To review the effectiveness, safety, and acceptability of first-trimester medical TOP, including medical treatment for incomplete miscarriage, by trained non-doctor providers. SEARCH STRATEGY AND SELECTION CRITERIA: A search strategy using appropriate medical subject headings was developed. Electronic databases (PubMed, Popline, Cochrane, CINAHL, Embase, and ClinicalTrials.gov) were searched from inception through April 2016. Randomised controlled trials and comparative observational studies were included. DATA COLLECTION AND ANALYSIS: Meta-analyses were performed for included randomised controlled trials regarding the outcomes of effectiveness and acceptability to women. Certainty of evidence was established using the GRADE approach assessing study limitations, consistency of effect, imprecision, indirectness and publication bias. MAIN RESULTS: Six papers were included. Medical TOP and medical treatment of incomplete miscarriage is probably equally effective when performed by non-doctor providers as when performed by doctors (RR 1.00; 95% CI 0.99-1.01). Women's acceptance, reported as overall satisfaction with the allocated provider, is probably equally high between groups (RR 1.00; 95% CI 1.00-1.01). CONCLUSION: Medical TOP and medical treatment of incomplete miscarriage provided by trained non-doctor providers is probably equally as effective and acceptable to women as when provided by doctors. TWEETABLE ABSTRACT: Medical termination of pregnancy performed by doctors and non-doctors can be equally effective and acceptable.

The Swedish Infant High-grade Reflux Trial - Bladder function.

INTRODUCTION: It has been suggested that infants with high-grade vesicoureteral reflux (VUR) have lower urinary tract dysfunction (LUTD) that is characterised by large bladder capacity (BC) and increased post-void residual (PVR). However, most of these infants have normal or small BC in early infancy and develop large capacity during the first year of life. OBJECTIVE: This study aimed to see whether LUTD development during the infant years in children with high-grade VUR could be prevented by early reflux resolution. MATERIALS AND METHODS: For early VUR intervention, endoscopic treatment (ET) was used in a randomised trial comprising 77 infants (55 boys) aged <8 months with VUR grade 4-5 (n = 30/n = 47); 39 were randomised to antibiotic prophylaxis and 38 to ET. Voiding cystourethrogram, free voiding observation (FVO) and renal scintigraphy were performed at baseline and after 1 year. Bladder capacity and PVR were obtained from FVO. LUTD was defined as a BC of ≥150% of expected and a PVR of ≥20 ml. RESULTS: There were no differences in bladder function variables seen between the treatment groups, despite significant differences in VUR resolution. Analysing bladder function related to VUR outcome (VUR grade ≤2 vs grade >2), independent of treatment, showed that VUR grade ≤2 was associated with a smaller BC at 1 year (P = 0.050) (a tendency already seen at baseline) and a lower PVR at baseline (P = 0.010). PVR increased from baseline to 1 year (P = 0.037) in children with grade ≤2 VUR (Summary Table). The group with persistent bilateral grade 5 VUR at 1 year had more abnormal bladder variables compared with other study subjects, with a tendency of larger BC (P = 0.057), higher PVR (P = 0.0073) and more LUTD (P = 0.029) at baseline and a larger BC at 1 year (P = 0.016). In explanatory analyses, using logistic regression, a high PVR at baseline was identified as a predictor of VUR grade >2 (P = 0.046), persistent bilateral grade 5 VUR (P = 0.022), recurrent urinary tract infection (P = 0.034), and only a tendency was seen regarding new renal damage (P = 0.053). CONCLUSION: There was no between-group difference seen in bladder function. In children with VUR resolution at follow-up, independent of treatment, BC decreased, whereas PVR increased. High PVR at baseline was a predictive factor for both non-resolution of high-grade VUR and recurrent urinary tract infection. The results suggest that LUTD cannot be prevented by early VUR resolution, but rather is an important prognostic factor for VUR outcome in both endoscopic and prophylactic treatment.

Radiological bladder characteristics in VCU for young children with high-grade VUR.

OBJECTIVES: It has been suggested that infants with dilating vesicoureteral reflux (VUR) often have lower urinary tract (LUT) dysfunction. Signs such as high voiding pressure levels, low bladder capacity and dyscoordination at voiding have previously been thought to be indicative of dysfunction. However, these findings have also been recognised in healthy infants and are, thus, not specific to dysfunction in this age group. The urodynamic findings of interest for LUT dysfunction in children with high-grade VUR have been shown to be high bladder capacity with incomplete emptying, and often with overactivity during filling. Because the bladders in children with VUR are often only investigated with voiding cystourethrography (VCUG) and not urodynamics, the question has arisen as to whether some of the urodynamic findings indicating dysfunction can be recognised as radiological signs. The aim of the present study was to evaluate whether cystometric signs of LUT dysfunction in infants with high-grade VUR could be recognised in VCUG. MATERIALS AND METHODS: One hundred and fifteen infants (80 boys) with Grades III-V VUR were included and investigated repeatedly with videocystometry (VCM) at a median age 6, 21 and 39 months. The sign looked for in the VCUG was bladder size (large, normal or small), according to the chosen levels in the bony pelvis. To validate the chosen levels for the different bladder sizes, bladder capacity data from a longitudinal study in healthy children were used. In addition, abnormalities in bladder wall/form and filling of the posterior urethra without voiding, as signs of bladder overactivity and detrusor-sphincter dyscoordination, were evaluated. RESULTS: Bladder size was estimated on VCUG as large, normal or small, according to pelvic landmarks. Large bladder size was mainly seen at the second and third evaluations (64% and 46%), whereas small capacity was mainly seen during the first year (33%). Corresponding cystometric capacities (ml) showed a significant difference between the groups of small, normal and large bladder size. The cystometric capacities of large and small bladder size were also compared with bladder capacity in healthy controls, where large had significantly higher bladder capacity versus age (P = 0.0001) and small had significantly lower (P = 0.011) bladder capacity versus age than in the healthy controls. Bladder shape/wall pathology was mainly seen during the first year (42%), combined with small capacity, and correlated to overactive contractions during filling. Moreover, filling of the posterior urethra without voiding, indicating detrusor/sphincter dyscoordination at voiding, was quite common during the first year (33%), and then successively decreased. CONCLUSIONS: The clinical implication from this study of small children with high-grade VUR was that a large bladder on VCUG was synonymous with a high-capacity bladder. According to earlier studies, this is a sign of LUT dysfunction in this age group and should therefore be an indicator for additional studies of bladder function. Overactive contractions could also be recognised in VCUG, but only at the infant evaluation, which should also be regarded as an indicator of LUT dysfunction. All other bladder VCUG signs mainly seen during early infancy were signs of immature bladder function and not a result of VUR dysfunction.

Effects of transcutaneous neuromodulation (TENS) on overactive bladder symptoms in children: a randomized controlled trial.

BACKGROUND: The aim of the present study was to investigate whether addition of transcutaneous electrical nerve stimulation (TENS) treatment improves the results of standard urotherapy in children with overactive bladder (OAB) symptoms. MATERIAL AND METHODS: Sixty-two children with symptoms of OAB and incontinence were included. The children were randomized either to standard urotherapy treatment alone or a combination of standard urotherapy and TENS. The effect variables were taken from a voiding-drinking diary: number of voiding, number of incontinence episodes, and maximum voided volume. RESULTS: Both treatment groups had good treatment results, with no significant difference between the groups. In the standard treatment group 13/28 (46%) were completely dry and 11/28 (40%) had a decrease in incontinence episodes, compared to 16/24 (67%) and 3/24 (13%), respectively, in the standard+TENS group (p=0.303). The number of voiding decreased in two-thirds of the patients in both groups. However, maximal voided volume only increased in the standard treatment group. Subjectively 72% and 80% considered themselves significantly improved or free of symptoms. Previous treatment was registered in 15/55 (27%). All efficacy variables decreased in those with previous treatment, but with no difference between the standard and standard+TENS treatment groups. The only difference noted was when comparing the children without previous treatment in the groups: a significantly higher proportion were completely dry in the TENS group (12/18 [71%] versus 10/22 [48%], p=0.05). CONCLUSION: Our results showed no significant difference overall in treatment response to OAB symptoms between urotherapy only and urotherapy+TENS, whereas a tendency to difference was found in children without previous treatment. Thus with good urotherapy support, TENS only seems to have marginal additional effects on OAB symptoms.

Genetic variations in VEGF and VEGFR2 and glioblastoma outcome.

Vascular endothelial growth factor (VEGF) and its receptors (VEGFR) are central components in the development and progression of glioblastoma. To investigate if genetic variation in VEGF and VEGFR2 is associated with glioblastoma prognosis, we examined blood samples from 154 glioblastoma cases collected in Sweden and Denmark between 2000 and 2004. Seventeen tagging single nucleotide polymorphisms (SNPs) in VEGF and 27 in VEGFR2 were genotyped and analysed, covering 90% of the genetic variability within the genes. In VEGF, we found no SNPs associated with survival. In VEGFR2, we found two SNPs significantly associated to survival, namely rs2071559 and rs12502008. However, these results are likely to be false positives due to multiple testing and could not be confirmed in a separate dataset. Overall, this study provides little evidence that VEGF and VEGFR2 polymorphisms are important for glioblastoma survival.

Treatment of bladder dysfunction and high grade vesicoureteral reflux does not influence the spontaneous resolution rate.

PURPOSE: We investigated whether the treatment of bladder dysfunction in infants with congenital high grade vesicoureteral reflux could influence the spontaneous resolution rate of the reflux and the number of recurrent urinary tract infections. MATERIALS AND METHODS: A total of 115 infants with high grade vesicoureteral reflux were included in a followup study of bladder function and reflux resolution between 1993 and 1999. The present study deals with 20 of these infants with mainly grade V reflux, most of whom had recurrent urinary tract infections in combination with high post-void residual and high bladder capacity. Treatment with clean intermittent catheterization was instituted during infancy in these 20 patients and continued until a median age of 4 years. RESULTS: Bladder capacity was high at presentation and at all followup investigations in the clean intermittent catheterization treated group. Moreover, residual urine was high at presentation and especially between ages 1 and 2 years. However, after bladder control was achieved this residual decreased and consisted mainly of reflux urine. In only 1 girl did reflux resolve spontaneously during the 4-year followup period. A total of 18 patients were treated surgically at the end of this period, and clean intermittent catheterization could be stopped a few months later in all but 2. Urinary tract infection recurrences were uncommon after the institution of treatment. CONCLUSIONS: The treatment of bladder dysfunction characterized by a high capacity bladder with poor emptying in infants with congenital high grade reflux does not influence the rate of spontaneous resolution. On the other hand, the tendency toward recurrent urinary tract infections appears to decrease with treatment.

Urinary bladder volume tracking using a Kalman filter.

This study introduced the Kalman filter procedure for tracking urinary bladder filling from intermittent bladder volume measurements taken by an ultrasonic bladder volume monitor. The Kalman filter was based on a double integrator as a model for the bladder filling process between micturitions and included a procedure to reset the filter in the event of a micturition. The performance of the Kalman filter was evaluated experimentally using an ultrasonic bladder volume monitor on seven male urologic patients. During cystometry, saline was infused into the patient's bladder at a constant rate of 30 ml min(-1) until it was full, and the volume of the bladder was recorded every 30 s by the bladder volume monitor. The evaluation showed that the filter significantly improved the precision of the measured volumes in terms of mean absolute errorby 4.2 ml (95% confidence interval: 0.7-7.7 ml) (p = 0.025) without affecting the system accuracy, i.e. slope (p= 0.92) and intercept (p= 0.32). Finally, the micturition reset procedure was verified using simulated data.

[The unknown history of lobotomy: women, children and idiots were lobotomized]. / Lobotomins okända historia: kvinnor, barn och idioter opererades.

The history of prefrontal lobotomy is an interesting example of medicine regarding as useful a treatment method which present-day consensus evaluates in a contrary fashion. A pilot study of archives from the Swedish state mental hospital Umedalen shows that the frequency of lobotomies as well as postoperative mortality were higher than what has earlier been assumed. The majority of the 704 patients who underwent lobotomy at Umedalen hospital were women. One unexpected finding concerns the numbers of mentally retarded patients and children who were subjected to lobotomy. Case records and other documents from the hospital archives indicate that the operation was performed largely for the benefit of the hospital rather than the patient, with an eye to engendering calm and order on the unruly wards.

The bone resorbing activity released by gingival fibroblasts isolated from patients with periodontitis is independent of interleukin-1.

Supernatants from gingival fibroblast cultures obtained from 14 patients with periodontal disease contained factor(s) capable of stimulating bone resorption in vitro, as assessed by the release of 45Ca from neonatal mouse calvariae. The possibility that the factor(s) was interleukin-1 alpha (IL-1 alpha), IL-1 beta or prostaglandin E2 (PGE2) was next investigated. The human fibroblast conditioned media (HFCM) stimulated PGE2 biosynthesis in bone. The stimulatory effect by HFCM on 45Ca release, however, was not affected by blocking prostaglandin biosynthesis with indomethacin. In contrast, 45Ca release induced by IL-1 alpha, IL-1 beta, thrombin and bradykinin was significantly reduced by indomethacin, whereas the effects of PTH and PTHrP were unaffected by indomethacin. The concentration of PGE2 in HFCM was too low to be solely responsible for the 45Ca release response. In addition, the amount of bone resorbing activity produced by the gingival fibroblasts was unaffected by cyclo-oxygenase inhibitors. Similar to IL-1 alpha and IL-1 beta, the stimulatory effect of HFCM was inhibited by gamma-interferon. HFCM did not stimulate cyclic AMP formation in the mouse calvarial bones. Antisera which specifically blocked human IL-1 alpha or IL-1 beta induced 45Ca release, and the specific IL-1 receptor antagonistic protein, did not inhibit the stimulatory effect of HFCM. These data show that gingival fibroblasts secrete bone resorbing factor(s) which is not due to IL-1 and which stimulates bone resorption by a prostaglandin- and cyclic AMP-independent mechanism.

Tissue necrosis after subgingival irrigation with fluoride solution.

Irrigation of periodontal pockets with fluoride solution after scaling and root planing is occasionally recommended to inhibit the growth of pathogenic bacteria in the periodontal pocket. At the same time, irrigation enables mechanical removal of loosely adhering plaque and debris. Due to its toxicity, fluoride solution deposited in the periodontium may lead to tissue damage. We report in this paper, a case of extensive periodontal tissue necrosis and permanent loss of alveolar bone after irrigation of periodontal pockets with stannous fluoride solution. The literature on the toxic effects of fluoride on the local tissues is briefly reviewed and arguments for a re-evaluation of the use of stannous fluoride for pocket irrigation are provided.

Postoperative analgesia with epidural bupivacaine and low-dose fentanyl--a comparison of two concentrations.

BACKGROUND: The purpose of the study was to compare the analgesic and side effects of two epidurally administered mixtures of bupivacaine and fentanyl with the same drug ratios. METHODS: One hundred patients scheduled for colorectal surgery were randomized to receive a thoracic epidural infusion of either bupivacaine 0.12% with fentanyl 2 micrograms/ml or bupivacaine 0.24% with fentanyl 4 micrograms/ml during 48 h postoperatively. The pumps were adjusted to keep the visual analogue scale (VAS) pain score at 3 or less (on a scale of 0-10) with a minimum of adverse effects. RESULTS: There were no statistically significantly differences between the two groups in VAS pain scores. The average VAS pain score resting varied between 0.5 and 1, and coughing between 1.9 and 3.4. One case of respiratory depression with breathing frequency 7 occurred in each group, but none of the patients required naloxone. One patient in the low concentration group developed partial motor weakness in both legs 36 h postoperatively. Equal drug amounts--bupivacaine 10.8-11 mg/h and fentanyl 18-18.4 micrograms/h--were given in both groups throughout the study. CONCLUSIONS: Both groups had low pain scores with few and comparable adverse effects. It thus seems that the volume is not important when mixtures of bupivacaine and fentanyl in the studies concentrations are infused epidurally at a low thoracic level. Practical reasons favour the higher concentration mixture.

Development of gingivitis around aged restorations of resin-modified glass ionomer cement, polyacid-modified resin composite (compomer) and resin composite.

Resin-modified glass ionomer cements (RMGIC) and polyacid-modified resin composites (PMC, compomers) are two recently introduced material groups supposed to replace traditional cements in operative dentistry. The new restoratives release initially fluoride in different relatively high concentrations, which decrease gradually during the first weeks in vivo. Earlier studies showed a stronger subclinical inflammatory reaction around different conventional tooth colored restorative materials than around intact enamel. The aim of this study was to compare intra-individually the initiation of gingival inflammation around, aged RMGIC, PMC and resin composite restorations. Subgingivally located Class III restorations were placed in 17 patients. Each patient received one of each of the experimental materials. All patients were placed on an oral hygiene regime 1-year after finishing of the restorations. Gingivitis was induced during a one-week period without oral hygiene. The gingival condition was assessed by sampling of gingival crevicular fluid (GCF), registration of the amount of bacterial plaque and by registration of bleeding after gentle probing of the entrance of the gingival sulcus (SBI) on the experimental filling- and control-enamel surfaces at days 0 and 7. No differences were seen in plaque and gingival index scores between the materials at both days. The GCF increased significantly for all surfaces during the experimental gingivitis period. At day 7 significantly lower GCF was sampled around the enamel surfaces. In conclusion, the differences between the materials did not result in measurable differences concerning clinical or subclinical signs of gingivitis.

Patient-controlled analgesia (PCA) with codeine for postoperative pain relief in ten extensive metabolisers and one poor metaboliser of dextromethorphan.

Postoperative pain relief with codeine was evaluated in 11 women undergoing hysterectomy. Patient-controlled analgesia (PCA) was used to administer codeine. After the study the patients were phenotyped with respect to the O-demethylation of dextromethorphan (cytochrome P4502D6 polymorphism). Ten were extensive metabolisers and one a poor metaboliser. There was a nine-fold variation in the minimum plasma concentration of codeine consistent with pain relief (40-350 ng ml-1). Two patients did not experience any effect of codeine, one of whom was a poor metaboliser of dextromethorphan, confirmed by genotyping. In the other nine patients the effective dose of codeine varied from 4.8-25.3 mg h-1.

The effect of glass ionomer cement and composite resin fillings on marginal gingiva.

Glass ionomer cement and composite resin are the most popular restorative materials in operative dentistry today. Earlier studies have shown more crevicular exudate around different types of composite resins than around intact enamel surfaces. The aim of this study was (1) to investigate plaque, retention on and the condition of the gingiva around, 1-year-old, subgingivally located, glass ionomer cement and composite resin fillings, and (2) to compare the initiation of gingival inflammation around these materials with that around enamel during a 14-day period of experimental gingivitis. Plaque index, gingival index, bleeding on probing and crevicular fluid were recorded and compared intra-individually. The amount of plaque and the degree of gingivitis adjacent to the composite fillings were not significantly higher than those for the glass ionomer cement and enamel surfaces in both the cross sectional and the experimental gingivitis study. Composite resin surfaces showed significantly higher crevicular fluid levels than did enamel at all days in the experimental gingivitis study. Glass ionomer cement showed significantly higher values at day-0 and day-7.

Presence of Streptococcus mutans and lactobacilli in saliva and on enamel, glass ionomer cement, and composite resin surfaces.

The quantity of S. mutans, total streptococci, and lactobacilli on sound enamel surfaces and 1-yr-old glass ionomer cement and composite resin fillings with the cervical margins placed subgingivally was compared intra-individually. The amount of bacteria was compared to their number in saliva. The evaluation was done in a cross sectional study, where the patients continued to use their customary oral hygiene procedures and during a 14-day period of experimental plaque formation. The number of lactobacilli and S. mutans recovered from the test surfaces indicated that the critical salivary concentrations necessary for the isolation of S. mutans and lactobacilli from glass ionomer cement and composite resin surfaces are the same as for the enamel surfaces. The fluoride levels in plaque adjacent to glass ionomer cement will not become high enough to inhibit the accumulation of the investigated bacteria.