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The total serum clearance of inulin after a single intravenous injection is an established method for the determination of the glomerular filtration rate (GFR). To optimize this procedure in children, we analysed 117 serum inulin time-decay curves in 59 children (age range 1·3-15·2 years) with renal disease. It was found that the two-compartment model fitted statistically better to the disappearance curves of serum inulin than the one-compartment model. The sampling frequency could be reduced from 12 to a minimum of seven data points (t = 0, 10, 20, 30, 65, 120 and 240 min) in 4 h without a relevant change in the fit of the two-compartment model to the data or in the calculated clearance of serum inulin. We conclude that, by using a standardized 'seven-sample schedule', followed by a two-compartment analysis, the single-injection serum clearance of inulin is a suitable compromise between practical convenience and clinical accuracy for the determination of the GFR in children.

The existence of a sexual problem as the subjective evaluation of sexual function was assessed with a simple questionnaire. Those questioned were patients undergoing dialysis treatment (n = 400) or with a functioning renal transplant (RTx; n = 300) and both men and women in the general Dutch population (n = 591). In the Dutch control population, 8.7% of the men and 14.9% of the women reported a sexual problem, showing a significant gender difference but unrelated to age. In patients, the prevalence of a sexual problem was significantly greater (hemodialysis, men, 62.9%; women, 75.0%; peritoneal dialysis, men, 69.8%; women, 66.7%; renal transplantation, men, 48.3%; women, 44.4%). In RTx recipients, sexual problems were significantly less prevalent than in patients undergoing dialysis (P < 0.001). Only in male patients was an association between prevalence of a sexual problem and age found. The results of the simple questionnaire were sufficiently validated when 102 of 104 patients confirmed their responses in a subsequent structured interview. This study shows that the prevalence of sexual problems in patients undergoing renal replacement therapy is high and clinically relevant.

In a randomized study, we analyzed the treatment results of ureterorenoscopy (URS) and shockwave lithotripsy (SWL) for extended-mid and distal ureteral stones. We investigated also, for reasons of cost effectiveness, the factors influencing the outcome, the complications, and the need for auxiliary procedures.In three regional hospitals, we selected 156 patients with extended-mid and distal ureteral stones. After randomization, 87 were treated with URS, and 69 with SWL. The treatment results were studied in relation to complications, the need for auxiliary procedures and stone factors, urinary tract infection (UTI), dilatation, and kidney function.After retreatment of 45% of the patients, the stone-free rate after 12 weeks in the SWL group was 51%. After a retreatment rate of 9% of the patients in the URS group, the stone-free rate was 91%. Including the number of auxiliary procedures, we calculated the Efficiency Quotient (EQ) as 0.50 for SWL and 0.38 for URS. After correction and redefinition of auxiliary procedures, the EQ was 0.66. The mean treatment time for SWL was 52 minutes and for URS 39 minutes. General anesthesia was more frequently needed in URS patients. Complications occurred more often in the URS group (22 v 3 and 24 v 13, respectively). These were mostly mild, and all could be treated with a double-J stent, antibiotics, or analgetics. A lower stone-free rate was achieved in patients with larger (or =11 mm) stones (75% v 85% for smaller stones in the URS group and 17% v 73% in the SWL group. In the URS group, the stone-free rate of patients with extended-mid ureteral stones was lower than that of patients with distal ureteral stones. Calculating the costs for URS and SWL appeared impossible because of the differences in available equipment.The stone-free rate after URS is much higher than after SWL, and the EQ in our series was strongly dependent on definitions. The decision about how to treat a patient with an extended-mid or distal ureteral stone therefore should not be made primarily on the basis of cost effectiveness but rather on the basis of the availability of proper equipment, the experience of the urologist, and the preference of the patient.

Reflex sympathetic dystrophy (RSD) is a disorder that can potentially result in permanent impairment. Because there are no adequate comparative studies regarding the additional value of physical therapy (PT) or occupational therapy (OT) for reducing the severity of permanent impairment in RSD, we prospectively investigated their effectiveness. At two university hospitals, we randomly assigned 135 patients with RSD of one upper limb, existing for

Objective: To study from a societal viewpoint the costeffectiveness of adjuvant treatment for patients with reflex sympathetic dystrophy (RSD) of one upper extremity. Design: A two-center randomized clinical trial comparing pairwise physical therapy (PT), occupational therapy (OT), and control treatment (CT). Patients: One hundred thirty-five patients with RSD for less than 1 year participated. Interventions: PT and OT were given according to protocols. For CT, services by social workers were offered. Main Outcome Measures: The Impairment-level Sum Score (ISS), the modified Greentest, and the Sickness Impact Profile (SIP) were used to determine effectiveness. Real medical costs, nonmedical costs, and productivity costs were distinguished and incremental cost-effectiveness ratios were calculated. Sensitivity analyses were performed on cost estimates. Results: The ISS, but not the Greentest and SIP, showed a significant difference between PT versus OT and CT. The mean adjuvant treatment costs were significantly higher for PT (Netherlands Guilders [NLG] 1,726) and OT (NLG 2,089) compared with CT (NLG 903). The mean total medical costs were not significantly different for the groups (PT, NLG 8,692; OT, NLG 13,023; and CT, NLG 7,888) (intention-to-treat analysis). The sensitivity analyses showed a moderate influence of the cost estimates. Conclusions: PT results in clinically relevant improvement in RSD. Costs associated with adjuvant treatment are moderate compared to other medical costs. The incremental costeffectiveness ratios of PT versus OT and CT were moderate or even dominant, thus PT was both more effective and less costly than its comparators.

An increased rate of obstruction of peritoneal dialysis catheters is observed during peritonitis. Hypercoagulation and hypofibrinolysis may explain this increased occurrence. We studied plasminogen activator inhibitor type 1 antigen (PAI-1), tissue-type plasminogen activator antigen (t-PA), D-dimer (DD), plasmin-alpha2-antiplasmin complexes (PAP), and thrombin-antithrombin III complexes (TAT) in 7 children with peritonitis (group A) and 12 children during stable peritoneal dialysis (group B). Albumin, beta2-microglobulin, IgG, and alpha2-macroglobulin were measured for baseline transperitoneal protein transport. After a dwell of 6 h with 1.36% Dianeal, dialysate and serum samples were collected. Dialysate to plasma ratios of all proteins were calculated. During peritonitis (group A) TAT was higher: 34.7 versus 22.0 (P=0.01). PAI-1 was increased in group A: 76.5 versus 22.9 (P=0.004). PAP was decreased during peritonitis (group A): 24.9 versus 39.3 (P=0.01). In group A, DD were decreased. 10.8 versus 26.7 (P=0.002). t-PA was similar in both groups (23.7 in group A vs. 27.7 in group B; P=0.26). In both groups TAT, PAI-1, t-PA, PAP, and DD were significantly higher than in baseline transperitoneal transport, suggesting intraperitoneal production. Hypercoagulability and hypofibrinolysis were present during peritonitis compared with the control situation.

In recent years, large discrepancies were described in the success rate of the tyrosinase reverse transcription polymerase chain reaction (RT-PCR) for detecting melanoma cells in the peripheral blood of melanoma patients. We present a quality control study in which we analysed the reproducibility of detection of tyrosinase and MART-1 transcripts in 106 blood samples from 68 melanoma patients (mainly stages III and IV). With this study, we aimed to improve insight in the reproducibility of a RT-PCR for the detection of (minimal) amounts of circulating melanoma cells. We performed two reverse transcriptions on each mRNA sample and performed tyrosinase and MART-1 nested PCRs in duplicate per cDNA sample. Thus, four tyrosinase and four MART-1 measurements were performed per blood sample. In our study, the majority of blood samples was negative for tyrosinase (80%) or MART-1 (66%). Only four samples were positive in all four determinations for tyrosinase and seven for MART-1. Variable results (1–3 times positive results) were obtained for tyrosinase and MART-1 in 16% and 27% respectively. MART-1 PCR had a better performance than tyrosinase PCR. Sensitivity increased when both markers were used. We reasoned that the low number of melanoma marker PCR-positive blood samples can be explained by differences in mRNA quality. By using real-time quantitative PCR, we found that this was not the case: amplification of porphobilinogen deaminase (PBGD), a low copy household gene, was not different in blood samples in which a melanoma marker was not detected from groups in which this marker was detected more or less consistently (1–4 times). When applying real-time quantitative PCR for tyrosinase and MART-1, we found that a low amount of SK-MEL-28 cell equivalents was present in the blood of melanoma patients, with a higher number of equivalents in the group with a consistently positive result. We conclude that low reproducibility of a repeated assay for the detection of circulating melanoma cells is not caused by differences in mRNA quality between the samples, but due to low numbers of amplifiable target mRNA molecules in the mRNA sample. Use of more than one marker and repetition of the assay will increase the probability of finding positive PCR results. © 1999 Cancer Research Campaign

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A methodological study was conducted to examine the effect of extending a frequently used simple multiattribute health-status classification system by adding a cognitive dimension. The EQ-5D questionnaire is a generic instrument to value health, developed by the EuroQol Group. The EQ-5D defines health according to five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. We defined 18 different health states according to the standard EQ-5D classification. A second set of health states was constructed similar to the first, except for the addition of a cognitive dimension (EQ-5D+C). Valuations of both sets of health states were statistically analyzed to detect the effect of the additional dimension. The cognitive dimension generated systematically different values compared with the standard EQ-5D version, whereas the content validity improved. Both systems evoked equally reliable values. Analyses showed that a simple additive model to predict summary values for health states was not optimal for both systems. Although there is a current lack of consensus regarding the domains that are selected to represent health status, this study has shown the importance of considering the inclusion of a cognitive domain.

In this randomized study, influences of dietary sodium restriction as an independent factor on anxiety levels of women participating in an in vitro fertilization-embryo transfer (IVF-ET) procedure were investigated. Anxiety levels of 119 women were measured using the Spielberger State and Trait Anxiety Inventory. Data of 69 women remained for analysis. Drop-outs, mainly due to cycle cancellations, tended to have higher mean state anxiety scores compared with women who continued (p = 0.11). Bias by selection affected both diet groups in similar proportions. State as well as trait anxiety scores increased significantly (p = 0.01, and p = 0.03, respectively) from baseline (before ovarian stimulation) to the point of measurement in the luteal phase. No significant differences in this mean increase were observed between the two diet groups. The significantly higher mean increase in state and trait anxiety in conceiving women was striking compared with those who did not conceive (p = 0.03 and p0.01, respectively). We conclude that dietary sodium restriction does not lower anxiety levels during an IVF-ET procedure. Anxiety levels increase more from baseline (before ovarian stimulation) to the luteal phase in conceiving than in nonconceiving women. The influence of conception on anxiety levels needs further investigation.

Objective . To determine the incidence and correlation of joint hypermobility (HM) and peripartum pelvic pain (PPPP) in an homogeneous pregnant South African population. Study design . A cross-sectional study among Cape Coloured pregnant women. Joint mobility was measured by Beighton score; PPPP with a specially developed PPPP score. Results . Using the Beighton scores with a cut-off point of HM≥5/9, only 4.9% of the 509 pregnant women were hypermobile. Hyperextension of the elbow was the largest contributor to HM (35.4%). No correlation of HM with the incidence of PPPP was established. Only 20 very mild cases of PPPP were recorded. Back pain increased significantly during pregnancy to a mean of 38%. Right handedness occurred in 95.9%. No significant relation was found between HM and the non-dominant side. Conclusion . Hypermobility in pregnant Cape Coloured women was surprisingly low (4.9%) with a decrease with age, but no increase during pregnancy. Peripartum pelvic pain is virtually absent and has no correlation with joint laxity. Back pain increased during pregnancy to a mean of 38%. Right handedness was high (96%) in comparison with the world-wide figure of 85%. No correlation was found between the dominant body side and hypermobility.

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Objective. To assess the effects of a Dutch national prevention programme, aimed at general practitioners (GPs), on the adherence to organizational guidelines for effective cervical cancer screening in general practice. To identify the characteristics of general practices determining success. Design. A prospective questionnaire study with pre- and post-measurement (before and 15 months after the introduction of the national programme). Setting and study participants. A random sample of one-third of all 4758 Dutch general practices. One GP was asked to participate per practice. Intervention. A national GP prevention programme to improve population-based prevention of cervical cancer combining various methods for quality improvement in general practice, performed on a national, district and practice level. Outreach visitors were a key strategy in bringing about behavioural changes. Main outcome measures. The proportion of practices adhering to 10 recommendations (in four guidelines) to organize effective cervical cancer screening. Results. After 15 months, all Dutch practices showed significant improvement in adherence to nine out of 10 recommendations. Two recommendations, in particular ‘identifying women who should be medically excluded from screening’ and ‘sending a reminder to non-compliers’ showed the largest absolute increases of 26% and 33%, respectively. Besides more intensive support of outreach visitors, practice characteristics such as ‘computerization’ and ‘delegation of many clinical tasks to the practice assistant’ were important in improving the adherence to guidelines. Conclusion. The national programme, with a combination of various methods for quality improvement, appeared to be effective in improving the organization of cervical screening in general practice. Computerization and, to a lesser extent, delegation of many clinical tasks to the practice assistant and more intensive support to practices, positively influenced the effectiveness of the national programme.

The aim of this prospective randomized controlled clinical trial was to evaluate and compare clinical aspects and satisfaction during the first year following treatment and consecutively the change in treatment during the next 4 years of follow-up. Patients were allocated to one of the following treatment modalities: an implant-retained overdenture (IRO-group, 2 endosseous implants, n = 61) or a complete denture (CD-group, n = 60). One year after placement of the denture, unsatisfied patients of the CD-group got the opportunity for a retreatment including an implant-retained overdenture. In the IRO-group 4 implants were lost during the first year and again 4 implants were lost during the next 4 years (survival rate: 93%). All patients could be re-operated successfully. In the CD-group 14 patients (23%) chose an implant-retained overdenture after 1 year. Patients of the IRO-group were significantly more satisfied than patients of the CD-group after 1 year (satisfaction score 8.3 versus 6.6, scale 1-10) and after 5 years (7.4 versus 6.4). From this study it can be concluded that endosseous implants have a high survival rate after 5-years' follow-up. Satisfaction score of the IRO-group is diminishing in time, probably because patients get used to an improved situation. After 5 years, the mean satisfaction score of the CD-group (including patients who got implants) was still lower than of the IRO-group, in spite of the opportunity to a retreatment and have implant-retained overdentures.

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Objectives : In this clinical trial, 180 veneer restorations (VRs) were evaluated. The purpose of the study was to collect survival data and to find possible relations between survival and (1) `type of VR', (2) `preparation design', (3) `operator' and (4) the patient-related variables `tooth-type' and `vitality of the tooth'. Methods : The restorations were provided by seven dentists in 112 patients on central and lateral maxillary incisors. Experimental variables were: `type of VR' (either direct resin composite (DC), indirect resin composite (IC) or porcelain (P)), `preparation design' (with and without incisal overlap) and `operator'. Failures were recorded at two levels: absolute failure (need for new restoration) and relative failure (need for repair). Survival was defined at three levels: (1) s!urvival of original restoration (S r , endpoints: `absolute' failures), (2) functional survival (S f , endpoints: `relative' failures) and (3) overall survival (S o , endpoints: both `absolute-' and `relative failures'). Results : The variable `type of VR' showed significant influence on S f and S o but not on S r . S f and S o rates of P, IC and DC were, respectively: S f -P, 94%; S o -P, 94%; S f -IC, 94%; S o -IC, 90%; S f -DC, 80%; S o -DC, 74%. VRs on vital teeth showed a significantly better survival than VRs on non-vital teeth at all survival levels. Conclusions : Preparation of the incisal edge for incisal coverage is considered to be unnecessary to assure or improve the strength of VRs. c non-vital teeth showed higher risk to fail than veneers placed on vital teeth. Porcelain veneers showed the best overall survival.

The aim of the present study was to assess the effect of normal growth and development on the Peer Assessment Rating index between 12 and 22 years of age. The sample consisted of 49 nonorthodontic subjects (24 male and 25 females) from the Nijmegen Growth Study. The mean age at the first observation was 12.2 ± 0.7 years and at the second observation 22.1 ± 0.6 years. The dental casts at these ages were scored with the Peer Assessment Rating index. The influence of the Angle classification and the treatment need on changes over time in the Peer Assessment Rating score were evaluated. The mean changes in the PAR scores over time between cases that have more than 30% improvement to those that have less than 30% improvement were calculated. The results indicate that there were no significant differences between the mean Peer Assessment Rating score at 12 years of age (12.20 ± 0.91) and at 22 years of age (12.45 ± 1.28), but there were relevant differences in individual cases. The changes were irrespective of the Angle classification or the treatment need. Changes over time in the weighted Peer Assessment Rating score were mainly correlated to changes in the anterior crossbite and the overjet. This correlation may be influenced, however, by the applied weighting factor for those occlusal traits. (Am J Orthod Dentofacial Orthop 1998;114:224-228)

Objective: To study the effect of sufficient energy intake, by means of the protocolized administration of naso-gastric tube feeding, on the nutritional status of a child with cancer. Design: A comparative experimental study. Setting: Tertiary care at the Centre for Pediatric Oncology, South East Netherlands, University Hospital, Nijmegen. Subjects: Seven children, newly diagnosed with cancer, were included in the experimental study and all completed the trial period. Fourteen patients were included in the retrospective study. They were randomly chosen from a group of patients previously treated for a malignancy at our department and who had received naso-gastric tube feeding for at least 16 weeks. Intervention: Protocolized (experimental group) vs non-protocolized (retrospective group) administration of naso-gastric tube feeding over a period of 16 weeks. The main difference was the amount of tube feeding administered. In addition to energy from other foods, children in the experimental group received 106±13% of their total daily energy requirements (TDER) by means of tube feeding, whereas children in the retrospective group had received 75±24%. Main outcome measures: Weight as a percentage of weight for height according to the 50th percentile of a healthy reference population=ideal weight. Results: Weight, expressed as a percentage of the ideal weight, increased significantly in the experimental group (18.2±8.4; P=0.01) and the retrospective study group (5.2±7.3; P=0.001). However, the increase was statistically significant in favour of the experimental group (P=0.003), in which all the children reached their ideal weight, compared to 21% in the retrospective group. Conclusion: Aggressive protocolized nutritional intervention during the intensive phase of anti-cancer treatment, in the form of naso-gastric tube feeding that provides the child’s total daily energy requirements, results in considerable improvement in the nutritional status.

Objective: The patient population undergoing myocardial revascularization has changed during the last few years. Knowledge of these changes, and of the subsequent influence on morbidity and:or mortality is important, not only for up-dating quality control, but also to support decision-making in financial and economical aspects, and in further research concerning coronary artery surgery. Methods: Pre-, per- and postoperative data of 3834 primary isolated coronary bypass operations, January 1987‐December 1995 were analyzed. The total group was divided into three time cohorts. Group A: 1987‐1989 (n 1292); group B: 1990‐1992 (n1130); and group C: 1993‐1995 (n 1412). Results: Mean age increased from 60.49 9.0 (S.D.) years in group A to 62.999.9 (S.D.) years in group C (PB0.0005). Patients with insulin-dependent diabetic (P 0.005), uro-nefrological (P0.002), pulmonary (PB0.0005)and neurological (P 0.003) pathology increased significantly, and there was a significant increase in the use of arterial grafts (PB0.05). Postoperative, hospital mortality remained stable (9 2.5%). However, there was a significant increasing percentage of patients with pulmonary (P 0.04), neurological (P 0.02) and uro-nefrological (PB 0.0005) problems. Conclusion: During the last few years there has been a trend in myocardial revascularization of older patients, with more coexisting disease. Despite the fact that hospital mortality seems stable, there is an increase in major postoperative morbidity. © 1998 Elsevier Science B.V. All rights reserved.

This paper describes the prevalence and severity of gingival recession in Tanzanian adults covering the age range from 20 to 64 years. In addition, it attempts to assess the relationship between the degree of gingival recession and the presence and amount of calculus. In the 20-34 years age group recession occurred in > or = 32% of the buccal, > or = 25% of the lingual, and > or = 13% of the approximal surfaces. These %s increased to > or = 64%, > or = 52%, and > or = 48%, respectively, in the 45-64 years age group. In the 20-34 years age group, lingual surfaces of mandibular incisors and canines followed by buccal surfaces of these teeth were the sites most severely affected with gingival recession. With increasing age, all sites became gradually more severely affected, particularly the buccal and lingual surfaces of the maxillary first molar. The lingual surfaces of mandibular incisors exhibited on an average 1.3 mm, 2.4 mm and 3.2 mm recession in the 20-34 years, 35-44 years and 45-64 years age group, respectively. Most of the correlation coefficients between gingival recession and calculus at the individual tooth surface in three age groups were statistically significant. The highest correlation coefficients (0.50-0.67) were found in the youngest (20-34 years) age group at the lingual surfaces of the mandibular incisors, canine and first premolar and at the buccal surfaces of the mandibular incisors. Based on these findings, the working hypothesis is advanced that longstanding calculus is an important determinant in the onset of gingival recession at sites exhibiting pronounced recession at a young age in populations deprived of prophylactic dental care.

The medical records of 66 surviving children born with congenital posterolateral diaphragmatic hernia (CDH) were reviewed to determine which factors are involved in the development of a recurrent hernia. Fifty-seven patients had a left-sided defect and 9 patients had a right sided defect. In 54 patients the defect was closed primarily and 12 patients required a prosthetic patch. Nine of the 66 patients (14%)--5 patients (9%) with a left-sided defect and 4 patients (44%) with a right-sided defect--developed a recurrent hernia on the average of 4.0 months (range 0.2-6.9) after the initial repair. Except for one, all patients with a recurrence presented with dyspnoea (n = 5) and/or feeding problems (n = 6). Of these 9 recurrences 4 patients (7%) had primary closure of the defect and in 5 patients (42%) a prosthetic patch was required. Four of the 11 patients (36%) who needed extracorporeal membrane oxygenation (ECMO) had a recurrence versus 5 patients (9%) who were conventionally treated. A hernial sac was found in 4 patients during the repair of the recurrent hernia. In 3 of them the initial defect was closed primarily. In conclusion, large-patch repaired defects and right-sided defects are risk factors for the development of a recurrent hernia. Furthermore the lack of a biological union between the sutured patch and the diaphragm tissue remnants is likely to be the cause of a reherniation. Meticulous inspection for a hernial sac during the initial operation could reduce the incidence of a reherniation.

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In 39 patients with acute meningococcal infections, the plasma concentrations of tumor necrosis factor-alpha (TNF) and its soluble receptors (sRs) TNFsR-p55 and TNFsR-p75 were measured from admission till recovery. At admission, patients with shock had significantly higher TNF, TNFsR-p55, and TNFsR-p75 values than patients without shock. In addition, during the first 24 hours, patients with shock had higher TNFsR-p75 to TNFsR-p55 ratios, indicating that in shock the increase of TNFsR-p75 exceeds that of TNFsR-p55. TNF measured more than 12 hours after admission failed to differentiate between shock and nonshock because TNF concentrations normalized within 12-24 hours. However, because concentrations of TNFsRs remained elevated for 5-6 days, at that time plasma TNFsRs still differentiated between shock and nonshock. Plasma exchange or whole blood exchange (PEBE), performed in 20 patients with shock, accelerated the decrease of plasma TNFsRs. However, because of a rebound after each PEBE session, the overall half-lives of both TNFsRs were not affected by PEBE.

Previous clinical observations have revealed that resin-bonded bridges for posterior tooth replacements are less retentive than anterior resin-bonded bridges. Improved bonding procedures and preparation designs, however, may have a positive effect on the functional durability of these restorations. The present study reports the final analysis of a randomized controlled clinical trial in which different designs of posterior resin-bonded bridges were evaluated for a period of at least 5 years. The operational hypothesis was that the bonding system and the preparation design used in posterior resin-bonded bridges have an influence on the survival and clinical functioning of these restorations. Survival in this study was defined at two levels: (1) 'complete' survival (survival without any debonding), and (2) 'functional' survival (survival including loss of retention on one occasion and successful rebonding of the original RBB without further debonding). With regard to 'complete' survival, no significant differences were found between the bonding systems used for adherence of the restorations to abutment teeth (etching/Clearfil F2, sandblasting/Panavia EX, and silica-coating/Microfill Pontic C). The variable 'preparation form' (conventional preparation form vs. modified preparation form) for complete survival was statistically in favor of the modified preparation form (62% vs. 46%), but did not influence the functional survival. With regard to 'functional' survival, the combination of silica coating and Microfill Pontic C was more retentive than the other bonding systems (90% survival vs. 72% and 75%, p < 0.01). Factor location was found to be highly significant for both survival levels [Cox's PH model, p = 0.0002 (Cox, 1972)]: The five-year 'complete' survival rates were 65% for maxillary restorations and 40% for mandibular restorations, while the five-year 'functional' survival rates were 89% and 68%, respectively. It is concluded that preparation of grooves in abutment teeth for posterior resin-bonded bridges is beneficial to their chance of survival. Resin-bonded bridges placed in the maxilla have a better prognosis than those made in the mandible. The bonding systems used in this study appear to have no influence on the chance of failure. In rebonded posterior resin-bonded bridges, the bonding system silica-coating/Microfill Pontic C was more retentive than the other systems tested.

A meta-analysis was performed on published data on the caries-inhibiting effect of fluoride gel treatment in 6- to 15-year-old children. The purposes of this meta-analysis were: (1) to calculate the overall caries-inhibiting effect of clinical fluoride gel treatment studies, based on explicit selection criteria, and (2) to explore factors potentially modifying the effect of fluoride gel treatment in caries prevention, concerning the baseline caries prevalence of the target population, the general fluoride regimen, and application features. The caries-inhibiting effect of fluoride gel application was assessed by the prevented fraction and the ‘number needed to treat’. The overal prevented fraction of the fluoride gel treatment studies, indicating the reduction of caries incidence by fluoride gel treatment relative to the incidence in the control group, was 22% (95% CI = 18–25%). Multiple regression analysis showed no significant influence on the prevented fractions for the variables ‘baseline caries prevalence’, ‘general fluoride regimen’, ‘application method’, and ‘application frequency’. The ‘number needed to treat’ (NNT), indicating the number of patients that need to be treated in order to prevent 1 DMFS, estimated the efficiency of fluoride gel treatment according to the caries incidence of the target population, including cost/effect relations. It was found that the NNT = 18 in a population with caries incidence 0.25 DMFS per year, and NNT = 3 in a population with caries incidence = 1.5 DMFS per year (treatment duration 1 year). From the standpoint of cost-effectiveness, the additional effect of fluoride gel treatment in current low and even moderate caries incidence child populations must be questioned.

1-Nitropyrene (1-NP) has been proposed as a marker for exposure to diesel exhaust particles (DEP). Since the extent of the actual intake of 1-NP adsorbed on DEP will be relatively low, sensitive and selective methods are needed regarding human exposure assessment. Two analytical methods are presented for the assessment of 1-NP metabolites in urine of male Sprague-Dawley rats administered a single intragastric dose of native DEP (SRM 2975, 20 mg, 35.7 microgram of 1-NP/g). Enzymatically hydrolyzed urine was extracted using Blue Rayon. The extracts were analyzed directly, using HPLC with postcolumn on-line reduction and fluorescence detection (HPLC-Flu), or were processed further for GC/MS/MS analysis. Although sensitive to several metabolites, the HPLC-Flu method lacked selectivity for quantitation of some important metabolites in rat urinary extracts, and therefore seems suitable for screening purposes only. With regard to GC/MS/MS analysis, derivatization with heptafluorobutyrylimidazole (HFBI) yielded low limits of determination for hydroxy-1-aminopyrenes, hydroxy-N-acetyl-1-aminopyrenes (converted to derivatized hydroxy-1-aminopyrenes by the reagent), and 1-aminopyrene (1.8-9.2 fmol on the column). Derivatization of hydroxy-1-nitropyrenes yielded relatively high limits of determination, and therefore, hydroxy-1-nitropyrenes were reduced to hydroxy-1-aminopyrenes prior to derivatization with HFBI. Intragastric administration of DEP to rats resulted in urinary excretion of 6-hydroxy-N-acetyl-1-aminopyrene, 8-hydroxy-N-acetyl-1-aminopyrene, 6-hydroxy-1-nitropyrene, 8-hydroxy-1-nitropyrene, and 3-hydroxy-1-nitropyrene (7, 1.2, 1.6, 0.3, and 0.5% of the dose within 12 h, respectively). 1-Nitropyrene, N-acetyl-1-aminopyrene, and 3-, 6-, and 8-hydroxy-1-aminopyrene were not observed as urinary metabolites following administration of a single dose of DEP. The observed excretion pattern and urinary metabolite concentrations suggest that 1-NP present on unmodified DEP becomes bioavailable to a large extent and is metabolized in the same way as was previously observed following administration of pure 1-NP. The presented methods are promising for assessment of human exposure to 1-NP, e.g., following exposure to DEP, because of the possibility of analyzing large volumes of urine, the conversion of three types of metabolites to one (the amino metabolites), and the low detection limits that are achieved.

Objectives: Attempts have been made to develop diagnostic methods which enable an early diagnosis of occlusal lesions which are not detectable by visual inspection. The aim of this study was to compare the performance of visual inspection focused on finding signs of fissure decalcification and discoloration, visual inspection upon fibre-optic transillumination (FOTI), and electrical conductance measurements (ECMs) in predicting the onset of occlusal caries in 6- and 11-year-old children. Methods : Fifty children aged 5–7 and 11–15 years, having first or second permanent molar teeth that were not exposed to the oral environment for more than half a year, participated in the study. Following baseline data recording, the diagnostic measurements were repeated six times at 6-month intervals over a period of 2.5 years. Results: Data were collected at predefined sites in the fissures. During the study, 220 of the 652 sites, i.e. 75 of 197 molars in 31 of the 50 children were judged to require a sealant or a sealant restoration. Two examiners jointly decided on the decay status at the sites. Survival plots showed that ECMs were superior to FOTI and fissure discoloration in predicting the onset of occlusal caries, although the differences were small. Conclusion: ECM is a better predictor of occlusal caries than fissure discoloration and FOTI, although the differences among the performance of the three methods in this study were very small. A cost-effective analysis is envisaged to obtain insight into the practical value of ECMs in the prediction of occlusal caries and, thus, into the effectiveness of sealant application.

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Summary The present investigation analyses longitudinally the effects of early orthopaedic and/or surgical treatment on maxillary alveolar arch development in 30 children with a complete bilateral cleft lip and palate (BCLP). Palatal arch dimensions were measured on dental casts and their growth velocities during different treatment periods were calculated. Differences in growth velocities between consecutive treatment periods were examined and tested statistically. Furthermore, growth velocities were compared with those of 80 non-cleft children. Before lip closure, growth of the intercanine width of children with a BCLP and non-cleft children was comparable. Only for arch length significantly was less growth observed in BCLP patients in comparison with the control group. After lip closure, intercanine width, arch length and segmental angle diminished. During the intersurgical period, arch form seemed to adapt to a new muscular balance. Immediately after soft palate surgery, growth of the intercanine width and intertuberosity width was restricted. This negative growth was compensated in the postsurgical period, where a catch-up growth of intertuberosity width was even observed.

One hundred and eighty-one consecutive patients with standard-risk leukaemia were transplanted with HLA-identical sibling grafts depleted of lymphocytes using counter-flow centrifugation. In 116 patients, standard conditioning was intensified by the addition of anthracyclines. Multivariate analysis revealed significantly more acute GVHD > or = grade 2 and a trend towards more chronic GVHD in patients conditioned with the addition of anthracyclines. For all patients the risk for chronic GVHD, but not for acute GVHD increased with a higher number of T cells in the graft. The projected 5-year probability of relapse was significantly lower in the group of patients conditioned with anthracyclines; 26% versus 52% (P = 0.015). In multivariate analysis the addition of anthracyclines to the conditioning regimen was the only significant factor contributing to a lower probability of relapse. The projected 5-year probability of leukaemia-free survival [LFS] in the patients conditioned with and without the addition of anthracyclines was 56% and 36%, respectively (P = 0.004). In multivariate analysis the addition of anthracyclines to the conditioning regimen correlated significantly with a lower number of mixed chimaeras in patients at 6 and 12 months after BMT. Mixed chimaerism at 6 months after transplantation did not significantly correlate with a higher incidence of relapse in further follow-up. In contrast, mixed chimaerism at 12 months after BMT was significantly associated with higher relapse rate. We conclude that the addition of anthracyclines to the conditioning regimen improves outcome of BMT using T-cell-depleted grafts.

In the Leuven Growth Study of Belgian Boys the growth and physical performance of Belgian boys followed longitudinally between 12 and 19 years were studied. Subsequently, a subsample (n = 240) of Flemish-speaking males were reexamined at 30 and 35 years. A first question relates to the individual growth patterns in a variety of physical fitness characteristics. The three strength tests (static, functional, explosive) show curves that are qualitatively similar to those for height and weight. Their adolescent spurts occur after the height spurt. Flexibility and the two speed tests appear to reach maximum velocities prior to the height and weight spurts. Longitudinal principal component analysis was applied to the study of growth patterns of several somatic and motor characteristics. The results for height show three components sufficient to provide an adequate representation of the original information. The first component characterizes the general position of an individual growth curve. Components 2 and 3 reflect fluctuation in percentile level during the age period studied and can be conceived as indices of stability and are related to age at peak height velocity (APHV) and peak height velocity (PHV), respectively. Relationships between somatic characteristics, physical performance, and APHV have been studied in a sample of 173 Flemish boys, measured yearly between +/- 13 and +/- 18 years and again as adults at 30 years of age. The sample was divided into three contrasting maturity categories based on the APHV. There are consistent differences among boys of contrasting maturity status during adolescence in body weight, skeletal lengths and breadths, circumferences, and skinfolds on the trunk. There are no differences in skinfolds on the extremities. None of the differences in somatic dimensions and ratios among the three contrasting maturity groups are significant at 30 years of age except those for subscapular skinfold and the trunk/extremity skinfold ratio. During adolescence, speed of limb movement, explosive strength and static strength are negatively related to APHV; thus, early maturers performed better than late maturers. However, between late adolescence and adulthood (30 years), the late maturers not only caught up to the early maturers, but there were significant differences for explosive strength and functional strength in favor of late maturers. Finally, age-specific tracking, using inter-age correlations, of adult health- and performance-related fitness scores were investigated. In addition, the independent contribution of adolescent physical characteristics to the explanation of adult fitness scores was also studied. Tracking between age 13 and age 30 years was moderately high (46% of variance explained) for flexibility, low to moderate (between 19% and 27% of variance explained) for the other fitness parameters and low for pulse recovery and static strength (7% to 11% of variance explained). Between age 18 and age 30 years the tracking was high for flexibility, moderately high for explosive and static strength, and moderate for the other fitness parameters except for pulse recovery. The amount of variance of adult fitness levels explained increased significantly when other characteristics observed during adolescence entered the regressions or discriminant functions.

Length and weight for age (1-12 months) charts are presented for the longitudinal Euro-Growth Study. "Weight-for-length", another widely used growth chart, presents a problem from a methodological point of view. Target length values (53-77 cm) are not observed in all infants, leading to truncated age distributions at most target lengths. It was demonstrated that the age at which the target length was reached (Fig. 8) had a significant influence on weight especially at a smaller length. This implies that the weight-for-length charts are biased. This phenomenon is due to the longitudinal measurement schedule at prechosen ages and not at prechosen lengths, which is impossible. To obtain the desired length-corrected weight standards, it is advocated to construct age-related body mass indices.

The objective of this study was to investigate the influence of blood transfusion and haemodilution on cerebral oxygenation and haemodynamics in relation to changes in cerebral blood flow velocity (CBFV) and other relevant physiological variables in newborn infants. Thirteen preterm infants with anaemia (haematocrit0.33) and ten infants with polycythaemia (haematocrit0.65) were studied during blood transfusion and haemodilution respectively using adult red blood cells and partial plasma exchange transfusion. Changes in cerebral concentrations of oxyhaemoglobin (cO2Hb), deoxyhaemoglobin (cHHb), total haemoglobin (ctHb), (oxidized-reduced) cytochrome aa3 (cCyt.-aa3) were continuously measured using near infrared spectrophotometry throughout the whole procedure. Simultaneously, changes of mean CBFV in the internal carotid artery were continuously measured using pulsed Doppler ultrasound. Heart rate, transcutaneous partial pressure of oxygen and carbon dioxide, and arterial O2 saturation were continuously and simultaneously measured. Blood transfusion resulted in increase of cO2Hb, cHHb, ctHb and red cell transport (product of CBFV and haematocrit), whereas CBFV decreased. The increase of cO2Hb exceeded that of cHHb, reflecting improvement of cerebral O2 supply. Haemodilution resulted in a decrease of cO2Hb, cHHb and ctHb, whereas CBFV increased. Red cell transport was unchanged. The decrease of cO2Hb exceeded that of cHHb, reflecting decreased cerebral O2 supply. cCyt.aa3 decreased after blood transfusion and remained unchanged after haemodilution, but the reliability of these results is uncertain. With the exception of a small, but significant increase in transcutaneous partial pressure of oxygen after blood transfusion, the other variables showed no changes. Each blood withdrawal during exchange transfusion resulted in only a significant increase in heart rate without changes in the other variables measured, suggesting unchanged cerebral perfusion.In newborn infants blood transfusion in anaemia results in improvement of cerebral oxygenation, but haemodilution in polycythaemia does not improve cerebral oxygenation despite possible improvement of cerebral perfusion.

To date, the identification of patients and carriers of the fragile X syndrome has been carried out by DNA analysis by means of the polymerase chain reaction and Southern blot analysis. This direct DNA analysis allows both the size of the CGG repeat and methylation status of the FMR1 gene to be determined. We have recently presented a rapid antibody test on blood smears based on the presence of FMRP, the protein product of the FMR1 gene, in lymphocytes from normal individuals and the absence of FMRP in lymphocytes from patients. Here, we have tested the diagnostic value of this new technique by studying FMRP expression in 173 blood smears from normal individuals and fragile X patients. The diagnostic power of the antibody test is 'perfect' for males, whereas the results are less specific for females.

Extracorporeal membrane oxygenation (ECMO) was incorporated in a strategy of delayed repair of congenital diaphragmatic hernia (CDH) and was used for preoperative stabilization in patients who were unresponsive to maximal conventional treatment. If ECMO was required for preoperative stabilization the diaphragmatic defect was repaired while the patient was on ECMO. In the early experience with this approach all patients suffered from bleeding complications. Therefore, we adopted the use of antifibrinolytic therapy with tranexamic acid (TEA) during and immediately after CDH repair on ECMO. The efficacy of TEA was studied in an unblinded study using historical controls by comparing the postoperative blood loss and the transfusion requirements of red blood cells (RBC) in patient groups treated without (n = 9) and with TEA (n = 10). Patients who received TEA had significantly less bleeding at the surgical site than patients not receiving TEA (57 v 390 mL, P = .005) and had significantly lower RBC transfusion requirements than patients not receiving TEA (1.13 v 2.95 mL/kg/h, P = .03). In the very first two patients of the TEA group we encountered fairly severe thrombotic complications. TEA may have contributed to those complications. Based on the authors' experience they conclude: (1) TEA is effective in reducing postoperative blood loss, hemorrhagic complications, and RBC transfusion requirements associated with CDH repair on ECMO. (2) TEA may be responsible for thrombotic complications. (3) The appropriate, empirically established, dosage and administration patterns of TEA for CDH repair during ECMO seem to be one bolus of 4 mg/kg TEA intravenously 30 minutes before the anticipated CDH repair and a continuous infusion of 1 mg/kg/h TEA during the 24 hours after CDH repair.

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Early indicators of the effectiveness of a screening test for chronic diseases such as breast cancer are the length of time the diagnosis is advanced by screening, the lead time, and the sensitivity of the screening test. This paper describes a model for simultaneously estimating the mean lead time and the sensitivity when only the number of cancers detected at the successive screenings and the number of cancers occurring in the time interval between the screening examinations are known. This model is particularly useful in assessing the effect of screening when the underlying cancer incidence in the screened group is unknown. The model is fitted to the data of 235 screen-detected breast cancer cases and 146 interval cancers diagnosed across 6 screening rounds of the program in Nijmegen. The maximum likelihood estimate for the mean lead time ranges from 1.3 years in the under age 50 group to 2.2 years in the age 50-65 group, both estimates having large confidence intervals. The corresponding sensitivity estimates are 0.92 and 1.00.

Ethyldeshydroxy-sparsomycin (EdSm) is a ribosomal protein synthesis inhibitor which synergistically enhances the antitumor activity of cisplatin against L1210 leukemia in vivo. Because cellular glutathione (GSH) and glutathione S-transferases (GST) are reported to interfere with the antitumor activity of cisplatin, we analyzed the effect of EdSm and cisplatin on GSH and GST activity in selected tumor cells. For this purpose we used three murine leukemia tumors with different sensitivities towards EdSm and cisplatin: L1210-WT, sensitive to both drugs, L1210-Sm, resistant to EdSm, and L1210-CDDP, resistant to cisplatin. No significant differences were detectable between these three cell lines regarding the population doubling time, the cell size, and the cellular level of protein and glutathione. Neither of the resistant L1210 subclones showed P-glycoprotein expression. Drug exposure, however, changed the intracellular dynamics. Exposure to EdSm strongly decreased the amount of cellular protein, decreased the overall GST activity and led to GSH depletion, whereas exposure to cisplatin induced a rise in the amount of protein, in GSH, and in the total GST activity. These effects are dose-dependent and correlate well with the sensitivity of the tumor cells for EdSm or cisplatin. In addition, exposure to EdSm lowered the V(max) of GST in L1210-WT and L1210-Sm; however, in L1210-CDDP both the V(max) and the K(m) were increased. That this was not a direct effect of EdSm on GST was shown in a cell-free system, where EdSm did not influence the GST activity nor could it act as a substrate for GST. Our results suggest that the synergistic combination of EdSm and cisplatin might be explained by EdSm switching off the cellular detoxification mechanism for cisplatin, i.e. by inhibition of de novo synthesis and subsequent depletion of GSH and GST.

Background. When determinants of nutrition guidance practices for primary care physicians (PCPs) are identified, the key question remains: what is the mechanism of action? This knowledge is essential in order to understand how PCPs practice nutrition guidance. Methods. Mail questionnaires (result of focus-group discussions and in-depth interviews) were sent to a nationwide random sample of 1,000 PCPs in the Netherlands, who had been in practice for between 5 and 15 years (633 respondents). The mechanism of action of determinants of nutrition guidance practices of PCPs was identified by means of linear structural relationship analysis (LISREL) using a postulated model. Results. The postulated model on the mechanism of action was confirmed. The model demonstrates that nutrition guidance practices of PCPs are directly and significantly based on a few predisposing factors; driving forces and perceived barriers may act as significant intermediary variables. The predisposing factors, driving forces, and perceived barriers were identified. Conclusion. Policies to improve nutrition guidance practices of PCPs may, in the future, benefit from a LISREL model analysis of determinants of these practices to become more effective. Using multiple regression analysis to ascertain the determinants of these practices could result in missing important predisposing factors and “hidden” intermediary factors and lead, therefore, to an incomplete understanding of the mechanism of action.

In a cross-sectional survey, plasma concentrations of alpha- and gamma-tocopherol, alpha- and beta-carotene (cis and trans isomers), lycopene, and retinol were determined by reversed-phase HPLC, and ratios of plasma alpha-tocopherol to cholesterol were calculated in 208 Swiss individuals ages 0.4-38.7 years. The influence of age, sex, and season of sampling was studied. Age was a significant predictor of all plasma concentrations except alpha-carotene. No sex-related differences were observed. Season of sampling affected alpha-tocopherol and retinol (higher in winter) and gamma-tocopherol and cholesterol concentrations (higher in winter and spring than in the other seasons). After correction for seasonal influences, age differences were 0.24 micromol/L per year for alpha-tocopherol, 0.04 micromol/L per year for retinol, and 0.04 micromol/L per year for cholesterol concentrations; ratios of plasma alpha-tocopherol to cholesterol were not affected by age. We constructed age-specific reference intervals from the regression line and a multiple of the standard deviation. Separate regression equations are presented for seasons with low and high values.

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summary Three types of veneer restorations (VRs) were evaluated for recognition by two groups of observers to study the aesthetic result. The different types of VRs were: porcelain, direct resin composite and indirect resin composite. One month after insertion of the VRs, colour transparencies were made of smiling patients randomly selected from a group of 112 patients participating in a clinical trial. The slides were evaluated by five dentists who were not familiar with the patients and by 25 beautician students (BS). Dentists were asked to locate the VRs which were present in the patients and to specify the type of VR. BS were only asked to locate the VRs. To trace a possible relationship between the aesthetic result of the treatment and a number of variables, ANOVA was applied to evaluate the variables:‘discolouration of the teeth’before treatment, ‘type of VR’ and ‘number of VRs’. Agreements in judgement were expressed in Cohen–Kappa coefficients. The results showed that the dentists could locate the VRs quite well (Kappa coefficient 0.64 ± 0.28) but for BS this was lower (Kappa coefficient 0.43 ± 0.27). The more VRs were made in one patient, the more difficult it was to locate them correctly. The other variables had no significant effect on the recognition of the VRs. It was not possible for the dentist observers to differentiate between the types of VRs.

The sensitivity of the mammographic screening test in the biennial screening program of Nijmegen is assessed by analyzing the occurrence of interval cancers, i.e. cancers surfacing clinically in the interval between a negative screening examination and the subsequent scheduled examination. The difference between the observed number of interval cancers and the expected number of clinically manifest cancers in the absence of screening for the interval period reflects the number of cancers detected by screening. The expected number should be limited by the number of those cancers that were not detectable at the time of the screening examination because their size was under the threshold of mammographic detectability (5 mm). In contrast to other sensitivity studies we took these 'fast growing' cancers into consideration, the numbers of which are estimated in each of the six-month periods of the two-year interval using age-specific tumor volume growth rates for three age groups:50, 50-69, andor = 70 years. In patients under age 50, the sensitivity was 64% for cancers which would become clinically manifest within one year after screening. This sensitivity was lower than those obtained from the 50-69 andor = 70 age groups, being 85% and 80%, respectively. For cancers that would become clinically manifest 12-18 months after screening, sensitivity decreases to 22% in the under age 50 group, and to 56% and 65% in the two above age 50 groups, respectively. We conclude that even when adjusted for growth rate, the mammographic screening test has a poor performance in the under age 50 group.