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Objectives To study short- and long-term effects of experiencing a disaster in repatriated injured survivors and the differential effect of injury, need for medical treatment, loss of loved ones and danger to life on both physical and mental health. Design Prospective online study. Setting Open online survey among Dutch survivors of the 2004 Asian tsunami. Participants Of the estimated total of 464 Dutch survivors, the authors recruited 144 unique respondents (59 men and 85 women) with a total of 175 assessments made in various time periods. Main outcome measures Health outcomes were Symptom Checklist 90 (SCL-90), Impact of Event Scale (original version, in Dutch) and Beck Depression Inventory II. Correlations were calculated with socio-demographic as well as disaster-related factors: physical injury, medical care, loss of loved ones and duration of threat to life. Assessments were clustered in four post-disaster time periods (0-3, 4-6, 7-30 and 31-48 months). Results Across these periods, SCL-90 scores were significantly higher than the reference population (p<0.001), with a significant linear downward trend between the groups over time (p=0.001). The same pattern occurred for the Impact of Event Scale (p<0.001) and the Beck Depression Inventory II (p=0.002). Physical injury, medical care or loss of loved ones was not associated with higher total SCL-90 scores or somatic subscores. Both duration of threat to life and female sex were correlated with all measured outcome parameters. Conclusions Exposure to the 2004 Asian tsunami had significant short- and long-term impacts on health complaints in a group of repatriated Dutch tsunami victims. Cross-sectionally, there was a trend towards recovery over 4 years, although 22% still reported high psychological and physical distress 4 years post-disaster. Duration of danger to life and female sex were associated with more physical and mental health complaints. In this study, neither disaster-related injury nor loss of loved ones resulted in negative health outcomes.

Purpose: To analyze endothelial cell density (ECD) decay after Descemet's stripping automated endothelial keratoplasty (DSAEK) and top hat keratoplasty (THPK) in patients with Fuchs' endothelial dystrophy (FED) and/or pseudophakic bullous keratopathy (PPBK)., Methods: Patients underwent either THPK (n = 33) or DSAEK (n = 39) at the Erasmus Medical Center, Rotterdam. For each nonrandomized cohort, a biexponential regression model for ECD decay was fitted. Factors associated with higher ECD decay were evaluated., Results: Median follow-up was 31.2 months (range, 11-91) in the THPK cohort, and 23.4 months (range, 6-61) in the DSAEK group. The early ECD decay was much higher after DSAEK (half time, 2.2 months) than after THPK (half time, 12.8 months). The late ECD decay after DSAEK was less steep (half time, 75.5 months) than after THPK (half time, 62 months). The 1-, 3- and 5-year endothelial cell losses derived from the models after DSAEK were 56%, 66%, and 73%, respectively, and after THPK were 24%, 50%, and 64%, respectively. For the DSAEK cohort, PPBK as an indication for surgery was associated with significantly higher late-phase decay rates. For the top-hat cohort, a significantly lower late-phase decay rate was found in PPBK. FED and same-session cataract surgery were confounding variables in the DSAEK cohort. Regarding DSAEK, postoperative re-bubbling was not found to have significant effects on early or late ECD decay rates. However, the small sample size and other limitations related to the method of evaluation may have influenced these findings., Conclusions: After DSAEK, early ECD decay was stronger than after THPK, as opposed to late decay. Late decay was faster for PPBK than for FED after DSAEK.

Background: Patients who undergo autologous femoropopliteal bypass surgery develop postoperative edema in the revascularized leg. The effects of intermittent pneumatic compression (IPC) to treat and to prevent postreconstructive edema were examined in this study., Methods: In a prospective randomized trial, patients were assigned to one of two groups. All patients suffered from peripheral arterial disease, and all were subjected to autologous femoropopliteal bypass reconstruction. Patients in group 1 used a compression stocking (CS) above the knee exerting 18 mmHg (class I) on the leg postoperatively for 1 week (day and night). Patients in group 2 used IPC on the foot postoperatively at night for 1 week. The lower leg circumference was measured preoperatively and at five postoperative time points. A multivariate analysis was done using a mixed model analysis of variance., Results: A total of 57 patients were analyzed (CS 28; IPC 29). Indications for operation were severe claudication (CS 13; IPC 13), rest pain (10/5), or tissue loss (7/11). Revascularization was performed with either a supragenicular (CS 13; IPC10) or an infragenicular (CS 15; IPC 19) autologous bypass. Leg circumference increased on day 1 (CS/IPC): 0.4%/2.7%, day 4 (2.1%/6.1%), day 7 (2.5%/7.9%), day 14 (4.7%/7.3%), and day 90 (1.0%/3.3%) from baseline (preoperative situation). On days 1, 4, and 7 there was a significant difference in leg circumference between the two treatment groups., Conclusions: Edema following femoropopliteal bypass surgery occurs in all patients. For the prevention and treatment of that edema the use of a class I CS proved superior to treatment with IPC. The use of CS remains the recommended practice following femoropopliteal bypass surgery.

Objective: To investigate the efficacy of A-V impulse technology (A-V) for oedema prevention and treatment following PTFE femoropopliteal surgery., Design: Prospective randomized clinical trial., Materials: 36 patients undergoing PTFE femoropopliteal bypass reconstructions, either being treated postoperatively with a compression stocking (CS) (Group-1, n = 19) or with A-V (Group-2, n = 17)., Methods: Patients in treatment group-1 used a CS postoperatively during 1 week day and night, patients in group-2 were treated with A-V postoperatively at night during one week. The lower leg circumference was measured preoperatively and at five postoperative time points., Results: Limb circumference has increased postoperatively on day 1 (CS 1.5%/A-V 1.4%), on day 4 (5.7%/6.3%), on day 7 (6.6%/6.1%), on day 14 (7.9%/7.7%) and on day 90 (5.8%/5.2%). Differences between treatment groups were not significant. A re-operation gives a significant 3.9% increase in circumference as compared to a first operation (95% CI: 1.5-6.4%; p = 0.002)., Conclusion: No significant differences were found in the extent of developed edema between the groups following PTFE femoropopliteal bypass surgery. A redo peripheral bypass operation results in significantly more postoperative oedema than a first-time performed bypass operation., (Copyright © 2010 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: Several variables have been studied as possible predictors for the efficacy of ECT, results from the few studies assessing the influence of age on the efficacy of ECT were inconsistent. In older patients suffering from severe depression, ECT is often the treatment of choice, therefore, investigating the influence of age on ECT response is considered relevant., Method: At two depression units, 141 patients meeting DSM-IV criteria for major depression and scores of at least 18 on the 17-item Hamilton Rating Scale for Depression (HAM-D) were treated with bilateral ECT, twice weekly. Clinical evaluation of depressive symptoms was performed each week; scores on the HAM-D were obtained 1-3 days prior to ECT and 1-3 days after termination of the ECT course. The primary outcome criterion was defined a priori as the mean change on the HAM-D score. The influence of age on mean change on the HAM-D score was analyzed with multiple linear regression analysis, adjusted for three covariables: center, duration of the index episode and presence of psychotic features., Results: Age as a continuous variable had no significant effect on the efficacy of ECT as measured by mean change on the HAM-D score (SE 0.057, p=0.84)., Limitations: The disproportionate distribution of patients among the three age groups appears to be the major limitation of the present study., Conclusion: This study suggests that the efficacy of ECT in elderly depressed patients is at least equal to that in younger depressed patients., (Copyright 2010 Elsevier B.V. All rights reserved.)

Background: Blood-retinal barrier breakdown secondary to retinal detachment and retinal detachment repair is a factor in the pathogenesis of proliferative vitreoretinopathy (PVR). We wished to investigate whether an estimated 700 to 1000 ng/ml subretinal dexamethasone concentration at the time of surgery would decrease the blood-retinal barrier breakdown postoperatively., Methods: Prospective, placebo-controlled, double blind clinical trial. In 34 patients with rhegmatogenous retinal detachment scheduled for conventional scleral buckling retinal detachment surgery, a subconjunctival injection of 0.5 ml dexamethasone diphosphate (10 mg) or 0.5 ml placebo was given 5-6 hours before surgery. Differences in laser flare photometry (KOWA) measurements taken 1, 3 and 6 weeks after randomisation between dexamethasone and placebo were analysed using mixed model ANOVA, while correcting for the preoperative flare measurement., Results: Six patients did not complete the study, one because of recurrent detachment within 1 week, and five because they missed their postoperative laser flare visits. The use of dexamethasone resulted in a statistically significant decrease in laser flare measurements at the 1-week postoperative visit., Conclusion: The use of a preoperative subconjunctival injection of dexamethasone decreased 1-week postoperative blood-retina barrier breakdown in patients undergoing conventional scleral buckling retinal detachment surgery. This steroid priming could be useful as a part of a peri-operative regime that would aim at decreasing the incidence of PVR.

Maintenance with a triple nucleoside reverse transcriptase Inhibitor (NRTI) regimen after successful induction with a dual NRTI/protease inhibitor (PI) combination may be advantageous, because of low pill burden, favorable lipids, and less drug interactions. This strategy to become free of PI-related problems without losing viral efficacy has not been formally tested. We performed a randomized, open-label, multicenter, 96-week comparative study in antiretroviral therapy (ART)-naïve patients with CD4 50 copies per milliliter). Two hundred seven patients had similar baseline (BL) characteristics: median CD4 180 cells/mm(3), median VL 5.19 log(10) copies per milliliter. One hundred twenty subjects (58%) met randomization criteria. Baseline VL differed significantly between dropouts and randomized subjects (median 5.41 versus 5.06 log(10) copies per milliliter, p = 0.017), as did CD4 cells (median 160 and 200 cells/mm(3), p = 0.044). Sixty-one subjects received TZV and 59 subjects continued NRTIs/PI. At week 48, 2 patients in the TZV group and 5 in the PI group did not have a sustained virologic suppression (log rank test; p = 0.379). CD4 counts increased significantly in both arms. In ART-naïve patients, TZV maintenance had similar antiviral efficacy compared to continued standard ART at 48 weeks after baseline. Patients on successful standard ART can be safely switched to a NRTI-only regimen, at least for the tested time period.

Depression and anxiety frequently occur together or in extension of each other. According to a previous study in depressed inpatients, a high trait anxiety level correlated with a positive response to the diazepam test (DT) and a low trait anxiety level with a negative response to the test. The aim of this study is to investigate whether positive reaction to the DT is related to a positive response to fluvoxamine and whether a negative reaction to the test is related to positive response to imipramine. The DT was performed in 130 patients diagnosed with a depressive disorder. Following the DT, the patients were randomly assigned to double-blind treatment with either imipramine or fluvoxamine. Doses of both antidepressants were adjusted to attain predefined blood levels, and the outcome was evaluated 4 weeks after attaining these blood levels. Twenty-two patients had a positive response to the DT, whereas 108 patients had a negative response. Although a positive DT is correlated with a high level of trait anxiety, no differences in depressive symptomatology and antidepressant response were found between patients with a positive and a negative DT.

The present study investigated the influence of gender and menopausal status on treatment response in depressed inpatients, treated with either imipramine or fluvoxamine. The patients were divided into three groups: men, premenopausal women and postmenopausal women. A multivariate analysis was performed using the difference in Hamilton score (pretreatment - post-treatment) for imipramine and fluvoxamine as dependent variable. The following independent variables were used: the baseline Hamilton score, the antidepressant used, the gender-group and the interaction between the type of antidepressant and gender. In total, 138 patients with a DSM IV diagnosis of depressive disorder were analysed. Men responded more favorably to imipramine (B = 7.12, P = 0.005). Premenopausal women had a better response rate to fluvoxamine than men (B = -8.66, P = 0.027). In depressed inpatients, men respond more favorably to imipramine than to fluvoxamine. Premenopausal women respond more frequently to fluvoxamine than men.

Background: Esomeprazole and pantoprazole are metabolized in the liver and the polymorphic CYP2C19 enzyme is involved in that process. This genetic polymorphism determines fast (70% of Caucasians), intermediate (25-30% of Caucasians) and slow (2-5% of Caucasians) metabolism of PPIs., Aim: To compare the acid-inhibitory effects of esomeprazole 40 mg and pantoprazole 40 mg at 4, 24 and 120 h after oral administration in relation to CYP2C19 genotype and pharmacokinetics., Methods: CYP2C19*2, *3, *4, *5 and *17 genotypes were determined in healthy Helicobacter pylori-negative Caucasian subjects. 7 wt/wt, 7 wt/*2, 2 wt/*17, 2 *2/*17 and 1 *2/*2 were included in a randomized investigator-blinded cross-over study with esomeprazole 40 mg and pantoprazole 40 mg. Intragastric 24-h pH-monitoring was performed on days 0, 1 and 5 of oral dosing., Results: A total of 19 subjects (mean age 24 years, 7 male) completed the study. At day 1 and 5, acid-inhibition with esomeprazole was significantly greater and faster than with pantoprazole. Differences in acid-inhibition and pharmacokinetics between wt/wt and wt/*2 genotype were significant for pantoprazole at day 1 and 5., Conclusions: Esomeprazole provides acid-inhibition faster than and superior to pantoprazole after single and repeated administration. The acid-inhibitory effect and the kinetics of pantoprazole are influenced by CYP2C19 genotype.

Purpose: To investigate the long-term effect of oral acyclovir administered during the first 6 months after penetrating keratoplasty (PK) for herpetic eye disease (HED)., Methods: A 5-year follow-up was undertaken for a patient population from a placebo-controlled, randomized trial on acyclovir prophylaxis after keratoplasty. In this former study the effectiveness of oral acyclovir prophylaxis was significant during the first 2 years after keratoplasty. Prospective data such as graft survival, graft clarity, vascularization, infective events, and rejection episodes were obtained from the national keratoplasty follow-up registry. Additional clinical data were derived from the medical charts., Results: For 47 of the original 63 enrolled patients, the 5-year follow-up was completed. Comparing the acyclovir group with the placebo group, we found that with regard to the cumulative clinically evident recurrences, there was a statistically significant lower monthly event rate in the acyclovir group (P = 0.037). There were no statistically significant differences in visual acuity or in the use of oral aciclovir between the two treatment groups. The incidences of graft failure, vascularization, and medication or surgery for glaucoma were too low to analyze differences between the two groups., Conclusion: The results of our study suggest that oral acyclovir prescribed during the first 6 months after PK for HED protects against clinically evident HED recurrences during the first 5 years following PK.

Objectives: To evaluate whether the level and duration of increased blood lactate levels are associated with daily Sequential Organ Failure Assessment (SOFA) scores and organ subscores and to evaluate these associations during the early and late phases of the intensive care unit stay., Design: Retrospective observational study., Setting: Mixed intensive care unit of a university hospital., Patients: 134 heterogeneous intensive care unit patients., Interventions: None., Measurements and Main Results: We calculated the area under the lactate curve above 2.0 mmol/L (lactateAUC>2). Daily SOFA scores were collected during the first 28 days of intensive care unit stay to calculate initial (day 1), maximal, total and mean scores. Daily lactateAUC>2 values were related to both daily SOFA scores and organ subscores using mixed-model analysis of variance. This was also done separately during the early (<2.75 days) and late (>2.75 days) phase of the intensive care unit stay.Compared with normolactatemic patients (n = 78), all median SOFA variables were higher in patients with hyperlactatemia (n = 56) (initial SOFA: 9 [interquartile range 4-12] vs. 4 [2-7]; maximal SOFA: 10 [5-13] vs. 5 [2-9]; total SOFA: 28 [10-70] vs. 9 [3-41]; mean SOFA: 7 [4-10] vs. 4 [2-6], all p < .001). The overall relationship between daily lactateAUC>2 and daily SOFA was an increase of 0.62 SOFA-points per 1 day.mmol/L of lactateAUC>2 (95% confidence interval, 0.41-0.81, p < .00001). During early intensive care unit stay, the relationship between lactateAUC>2 and SOFA was 1.01 (95% confidence interval, 0.53-1.50, p < .0005), and during late intensive care unit stay, this was reduced to 0.50 (95% confidence interval, 0.28-0.72, p < .0005). Respiratory (0.30, 0.22-0.38, p < .001) and coagulation (0.13, 0.09-0.18, p < .001) subscores were most strongly associated with lactateAUC>2., Conclusions: Blood lactate levels were strongly related to SOFA scores. This relationship was stronger during the early phase of intensive care unit stay, which provides additional indirect support for early resuscitation to prevent organ failure. The results confirm that hyperlactatemia can be considered as a warning signal for organ failure.

With respect to the pharmacological characteristic, venlafaxine is comparable with tricyclic antidepressants (TCAs), and venlafaxine might be comparable in efficacy. We performed a systematic review investigating the relative efficacy and tolerability of venlafaxine compared with TCAs (imipramine, clomipramine, amitriptyline, nortriptyline and desipramine). Relevant double-blind randomised trials were identified from systematic searches of electronic databases. An exact analysis of the estimated odds ratios of response of the TCA relative to venlafaxine showed no overall significance of treatment effect (P = 0.38). The odds ratios were not homogenous across studies (P = 0.0213). The average dose of venlafaxine was 103.5 mg/day and for the TCA 106.1 mg/day. An exact analysis of the estimated odds ratios of the withdrawals and side effects in the trials with a TCA relative to venlafaxine showed no overall significance of withdrawal. From our review, no significant difference in treatment effect between low dose of both venlafaxine and the TCAs could be found. In our opinion, because of the heterogeneity of the odds ratios, one cannot conclude that they are of equal efficacy.

Summary: In women older than 60 years with clinical risk factors for osteoporosis but without osteoporosis based on bone mineral density (T-score >or= -2.5), a systematic survey with X-rays of the spine identified previously unknown vertebral deformities in 21% of women., Introduction: This study determines the prevalence of vertebral deformities in elderly women with clinical risk factors for osteoporosis but with BMD values above the threshold for osteoporosis (T-score >or= -2.5)., Methods: Bisphosphonate naïve women older than 60 years attending 35 general practices in the Netherlands with >or=2 clinical risk factors for osteoporosis were invited for BMD measurement (DXA). In women with T-score >or= -2.5 at both spine and the hips, lateral radiographs of the thoracic and lumbar spine were performed., Results: Of 631 women with a DXA measurement, 187 (30%) had osteoporosis (T-score < -2.5 at the spine or the hip). Of the remaining 444 women with T-score >or= -2.5 at both spine and hip, 387 had additional spine radiographs, of whom 80 (21%) had at least one vertebral deformity., Conclusion: In elderly women with clinical risk factors for osteoporosis but BMD T-score >or= -2.5, addition of spine radiographs identified vertebral deformities in 21% (95% CI: 17-25). Since these women are at risk of future fractures, antiosteoporotic treatment should be considered.

Background: Skin lesions are the predominant clinical feature of the commonest form of mastocytosis. Mastocytosis is classified according to World Health Organization criteria. Determination of the levels of mast-cell mediators or their metabolites reflects the mast-cell burden. The extent of cutaneous mastocytosis can be assessed clinically using a scoring system (SCORing MAstocytosis; SCORMA Index) that we have developed., Objective: Serum tryptase levels were compared with the SCORMA Index in a large group of paediatric and adult patients to investigate whether there was any correlation between the two., Methods: The SCORMA Index in 64 patients (31 children and 33 adults) was compared with serum tryptase levels. The results of the first visit at which SCORMA and tryptase were evaluated were analysed., Results: There was a positive correlation between the SCORMA Index and serum tryptase levels, indicating the value of the SCORMA Index in the assessment of mastocytosis with skin involvement., Conclusion: The results of this study showed that the SCORMA Index is a useful tool for evaluating the severity of cutaneous mastocytosis. The correlation between the SCORMA Index and serum tryptase levels underlines the benefit of the SCORMA Index as a clinical tool. Repeated SCORMA Index measurements can provide a rapid impression of changes in the clinical state of mastocytosis. This is particularly relevant in children, because taking blood samples from this group is much more difficult. The well-established methods for evaluation of disease severity may be expanded by the rapid SCORMA Index method.

The boll weevil, Anthonomus grandis grandis Boheman (Coleoptera: Curculionidae), is a serious pest of cultivated cotton, Gossypium hirsutum L., in the Americas, and reinfestation of zones from which they have been eradicated is of perpetual concern. Extensive arrays of pheromone traps monitor for reintroductions, but occasionally the traps collect nontarget weevils that can be misidentified by scouts. For example, the congeneric pepper weevil, Anthonomus eugenii Cano, and other superficially similar weevils are attracted to components of the boll weevil lure or trap color. Although morphologically distinguishable by trained personnel, the potential for misidentification is compounded when captured weevils are dismembered or partially consumed by ants or ground beetles that sometimes feed on them in the traps. Because misidentification can have expensive consequences, a molecular diagnostic tool would be of great value to eradication managers. We demonstrate that a cocktail of three primer pairs in a single polymerase chain reaction (PCR) amplify species-specific microsatellites that unambiguously distinguish the boll weevil from three other weevil species tested, including pepper weevil; cranberry weevil, Anthonomus eugenii musculus Say; and pecan weevil, Curculio caryae Horn. However, it does not distinguish the boll weevil from the subspecific "thurberia" weevil. A universal internal transcribed spacer primer pair included in the cocktail cross-amplifies DNA from all species, serving as a positive control. Furthermore, the diagnostic primers amplified the target microsatellites from various boll weevil adult body parts, indicating that the PCR technology using the primer cocktail is sensitive enough to positively identify a boll weevil even when the body is partly degraded.

Objective: To investigate the reliability of length measurements of the mandible by comparing orthopantomograms (OPTs) with lateral cephalograms., Design: Observational study., Setting: OPTs and lateral cephalograms were taken of 20 human dry skulls. Four orthodontists and four maxillofacial surgeons located landmarks on all radiographs using a computer program for cephalometric measurements. Intraobserver and interobserver variability in locating landmarks was assessed, as well as positioning of the skulls prior to radiography between the x-ray assistants. Magnification differences between the left and right side of the mandible on the OPT were determined for five skulls. Kappa statistics were used to calculate the intraclass correlation coefficient for intraobserver and interobserver differences. An F test was used to assess differences between methods and between type of observer., Results: No significant differences were found in the magnification factor of the left and right side of the mandible. Compared with a lateral cephalogram, the OPT had comparable reliability in measuring mandibular distances condylion-gonion, gonion-menton, and condylion-menton. No significant differences were observed between the x-ray assistants in taking the OPTs and lateral cephalograms or in repositioning the skulls. Significant differences were found between orthodontists and maxillofacial surgeons for landmark measurements., Conclusion: An OPT is as reliable as a lateral cephalogram for linear measurements of the mandible (condylion-gonion, gonion-menton, and condylion-menton).

Unlabelled: Comparing different types of calcaneal fractures, associated treatment options, and outcome data is currently hampered by the lack of consensus regarding fracture classification. A systematic search for articles dealing with calcaneal fracture was performed, and the prevalence of use of each classification system determined. Twelve observers classified 30 intra-articular calcaneal fractures according to the 3 most prevalent classification systems; interobserver reliability (kappa [kappa] statistic) and the correlation of the system with the choice of treatment and clinical outcomes were calculated. Forty-nine conventional and 15 computerized tomographic scan classification systems were identified. The most prevalent systems were the Essex-Lopresti, Zwipp, Crosby, and Sanders classifications; and none of these showed a direct correlation with treatment, although each of these systems showed positive correlations with outcome. Moderate interobserver agreement and variability were found for the Crosby and Sanders classifications (overall kappa = 0.48), whereas interobserver reliability among radiologists was poor for the Essex-Lopresti classification (overall kappa = 0.26). Four classifications systems showed positive correlations with outcome, but no correlation with choice of treatment. The Sanders and Crosby classifications displayed comparable, moderate interobserver variability among surgeons and radiologists, and both of these systems are likely to be useful for classification of intra-articular calcaneal fractures., Level of Clinical Evidence: 5.

In recent years, the atopy patch test (APT) has been suggested as an addition in the allergological work-up of children with atopic dermatitis (AD) and suspected food allergy. We initiated a prospective clinical study in children with AD younger than 3 yr, to evaluate the additional clinical value of the APT next to our own standardized allergological work-up in case of a suspected food allergy. One hundred and thirty-five children were included in the study. They were tested using the skin application food test (SAFT), the APT and measurement of specific IgE. The allergens used in the skin tests were freshly prepared food stuffs and included commercially available cow's milk (CM), the egg white of a hard boiled hen's egg and mashed peanuts in a saline solution. Allergy was defined using a flowchart incorporating the results from the SAFT, oral challenges (OCs) and elimination and (re)introduction periods. To determine the additional value of the APT next to the SAFT, we analyzed the SAFT negative patients per allergen and used an exact binary logistic analysis to evaluate the simultaneous effects of the APT and measurement of specific IgE, calculating mutually adjusted odds ratios (ORs) for positive APTs and specific IgE levels above 0.70 U/l. We found clinically relevant food allergies in 23% (egg white) to 28% (CM and peanut) of our study population. Positive SAFT reactions were observed in 14% (peanut), 16% (egg white) and 21% (CM) of our patient population. Next to the SAFT, we did not observe a significant additional value of the APT for the diagnosis of CM or egg white allergy, but we did find a significant additional value for the diagnosis of peanut allergy (OR = 11.56; p < 0.005, 2-sided). In clinical practice this statistically significant value does not exclude the need for OC and controlled elimination and (re)introduction periods due to the presence of false-negative as well as false-positive results in the APT. In conclusion, we could not find enough support for the current addition of the APT to our standardized allergological work-up in young children below the age of 3 yr with AD and suspected food allergy. At the moment the additional value of the classical delayed-type APT next to the SAFT seems to be very limited at best in this study population and does not justify the time-consuming nature of the skin test.

Background: Besides short stature, gonadal dysgenesis leading to a lack of oestrogen is one of the main characteristics of Turner syndrome (TS). In most TS girls, puberty is induced with exogenous oestrogens., Objective: To describe the pubertal development and uterine dimensions achieved by low-dose 17beta-oestradiol (17beta-E2) orally started at an appropriate age. Additionally, to determine whether serum hormone levels aid evaluation of pubertal progression., Design: In 56 TS girls, we prospectively studied pubertal stage, serum E2, LH, FSH, SHBG and oestrone (E1), starting oestrogen treatment with a low-dose 17beta-E2 (5 microg/kg/day) during GH treatment at mean (SD) age 12.7 (0.7) years. Hormone levels were measured at start, 3 months after start and after increasing 17beta-E2 dosage. Uterine dimensions were measured in 39 TS women at age 19.9 (2.2) years., Results: Although breast and pubic hair development were similar to that in normal Dutch girls up to Tanner stage B5 and P5, respectively, breast development was 2 years later. Before oestrogen therapy, E2 levels were comparable to those in prepubertal girls. With a 17beta-E2 dose of 5 microg/kg/day, these levels increased significantly, becoming comparable to normal late pubertal or adult concentrations, whereas SHBG levels were unchanged. At the adult 17beta-E2 dose, SHBG had increased significantly. Uterus shape was juvenile in four (10.2%), cylindrical in four and mature-adult shaped in 31 (79.5%) of TS patients., Conclusions: During GH treatment in TS girls, normal breast development up to B5 can be mimicked, with just a 2-year delay. In a clinical setting, serum hormone levels provide no additional information for evaluating pubertal progression. After age-appropriate pubertal induction, uterine dimensions in women aged nearly 20 years were subnormal. It remains unclear whether this was related to E2 dosage, timing or duration, or factors related to TS.

Objective: Compare duration of mechanical ventilation (MV), weaning time, ICU-LOS (ICU-LOS), efficacy and safety of remifentanil-based regimen with conventional sedation and analgesia., Design: Centre randomised, open-label, crossover, 'real-life' study., Setting: 15 Dutch hospitals., Patients: Adult medical and post-surgical ICU patients with anticipated short-term (2-3 days) MV., Interventions: Patient cohorts were randomised to remifentanil-based regimen (n = 96) with propofol as required, for a maximum of 10 days, or to conventional regimens (n = 109) of propofol, midazolam or lorazepam combined with fentanyl or morphine., Measurements and Main Results: Outcomes were weaning time, duration of MV, ICU-LOS, sedation- and analgesia levels, intensivist/ICU nurse satisfaction, adverse events, mean arterial pressure, heart rate. Median duration of ventilation (MV) was 5.1 days with conventional treatment versus 3.9 days with remifentanil (NS). The remifentanil-based regimen reduced median weaning time by 18.9 h (P = 0.0001). Median ICU-LOS was 7.9 days versus 5.9 days, respectively (NS). However, the treatment effects on duration of MV and ICU stay were time-dependent: patients were almost twice as likely to be extubated (P = 0.018) and discharged from the ICU (P = 0.05) on day 1-3. Propofol doses were reduced by 20% (P = 0.05). Remifentanil also improved sedation-agitation scores (P < 0.0001) and intensivist/ICU nurse satisfaction (P < 0.0001). All other outcomes were comparable., Conclusions: In patients with an expected short-term duration of MV, remifentanil significantly improves sedation and agitation levels and reduces weaning time. This contributes to a shorter duration of MV and ICU-LOS.

Objective: Lamotrigine is one of the pharmacologic options for the treatment of bipolar depression but has only been studied as monotherapy. This study compared the acute effects of lamotrigine and placebo as add-on therapy to ongoing treatment with lithium in patients with bipolar depression., Method: Outpatients (N = 124) aged 18 years and older with a DSM-IV bipolar I or II disorder and a major depressive episode (Montgomery-Asberg Depression Rating Scale [MADRS] score > or = 18 and Clinical Global Impressions-Bipolar Version [CGI-BP] severity of depression score > or = 4) while receiving lithium treatment (0.6-1.2 mmol/L) were randomly assigned to 8 weeks of double-blind treatment with lamotrigine (titrated to 200 mg/d) or placebo. The primary outcome measure was mean change from baseline in total score on the MADRS at week 8. Secondary outcome measures were response (defined as a reduction of > or = 50% on the MADRS and/or change of depression score on the CGI-BP of "much improved" or "very much improved" compared to baseline) and switch to mania or hypomania (defined as a CGI-BP severity of mania score of at least mildly ill at any visit). Patients were included in the study between August 2002 (Spain started in October 2003) and May 2005., Results: Endpoint mean change from baseline MADRS total score was -15.38 (SE = 1.32) points for lamotrigine and -11.03 (SE = 1.36) points for placebo (t = -2.29, df = 104, p = .024). Significantly more patients responded to lamotrigine than to placebo on the MADRS (51.6% vs. 31.7%, p = .030), but not on the CGI-BP change of depression (64.1% vs. 49.2%, p = .105). Switch to mania or hypomania occurred in 5 patients (7.8%) receiving lamotrigine and 2 patients (3.3%) receiving placebo (p = .441)., Conclusion: Lamotrigine was found effective and safe as add-on treatment to lithium in the acute treatment of bipolar depression., Trial Registration: clinicaltrials.gov Identifier: NCT00224510., (Copyright 2009 Physicians Postgraduate Press, Inc.)

Treatment of atopic dermatitis (AD) in children tends to stabilize the condition in the short term. 'Maintenance' treatment options in children are limited. To assess the efficacy and safety of twice daily treatment with fluticasone propionate 0.005% (FP) ointment during 4 wk and the efficacy and safety of twice weekly maintenance treatment with FP in preventing exacerbations or remissions of AD during a 16 wk follow-up period. Ninety children (aged 4-10 yr) with moderate to severe AD were included in a randomized, multi-centre study and received FP ointment twice daily during the acute phase. Children whose AD was in remission after 4 wk of treatment, entered the maintenance phase. In addition to twice daily emollient, children were randomly allocated to receive FP or placebo ointment twice weekly on consecutive days. Efficacy was assessed by the objective SCORAD. Eighty-seven (97%) completed the 4-wk acute study period. Extensive remission was achieved in 78 (87%) children, and 75 children entered the maintenance phase. Intermittent treatment with FP resulted in less severe AD and significantly reduced risk of further relapse as compared with placebo. The risk of an exacerbation of AD was more than twice as high in the placebo group as in the FP group (hazard ratio 2.182, 95% CI). AD in girls was better controlled than in boys. This long-term study shows that the addition of twice weekly FP to standard maintenance therapy significantly reduces the risk of relapse in children with moderate severe AD.

Background: Depression can occur in patients with or without trait anxiety. Although it is assumed that assessment of defenses can be useful in planning biological treatment, no studies have confirmed this hypothesis. In this study we focus on the relation between trait anxiety and defensive functioning, and on the combined influence of these personality characteristics on response to antidepressants among inpatients with a major depressive episode., Methods: Major depressive episode was diagnosed using the Schedule for Affective Disorders and Schizophrenia (SADS) and the severity of the depression was measured with the Hamilton Rating Scale for Depression (HAM-D). The level of trait anxiety was assessed using a questionnaire with 34 questions pertaining to trait anxiety. The Defense Style Questionnaire (DSQ 88) was used to assess defensive functioning followed by a weighted overall defensive functioning score (ODF). Partial correlations and multiple regression analyses were used to analyze the data., Results: The final sample included 85 patients. A significant negative effect of trait anxiety by ODF (p: 0.000) was found on the outcome score, i.e. the combination of a high score on trait anxiety and a low score on the ODF resulted in a significantly higher final score on the HAM-D., Conclusions: The most important finding in this study is that the combination of a high level of trait anxiety and immature defensive functioning evidently had a negative effect on antidepressant treatment outcome., (Copyright 2009 S. Karger AG, Basel.)

Aims: To investigate whether long-term growth hormone (GH) treatment influenced blood pressure (BP), body proportions and BMI in young Turner syndrome (TS) women several years after GH discontinuation., Methods: A follow-up study of a randomized GH dose-response trial with 3 GH dosages (1.3, 2.0, and 2.7 mg/m(2)/day). 39 TS patients (20.0 +/- 2.1 years) participated 4.8 (1.9) years after GH discontinuation. Mean GH duration was 8.7 (2.0) years., Measurements: BP, BMI and body proportions., Results: During GH treatment, DBP had decreased. At the long-term follow-up study, DBP had increased and was similar to pretreatment levels. DBP was negatively influenced by GH dose. SBP was not influenced by GH dose or duration. The BMI increased gradually during and after GH therapy. During GH therapy, shape values of sitting height had decreased to normal values, of foot had increased, and both remained constant after GH discontinuation., Conclusions: GH therapy in girls with TS has, besides height, additional beneficial effects on BP and body proportions, except foot length. Nearly 5 years after ending GH, the favorable effect of GH on BP was still noticeable. The BMI increased gradually over the years, not influenced by GH., (2009 S. Karger AG, Basel)

Background: Culture can have a considerable influence on the way in which a depression is experienced, expressed or presented. Strict Calvinists or reformed pietists form an orthodox protestant cultural minority in the Netherlands. This orthodox wing of the Dutch Reformed Churches places a strong emphasis on personal religious experience of God's work of conversion. It is possible that symptoms of depression in this group differ somewhat from such symptoms in nonaffiliated depressed patients., Aim: To determine whether depressive symptoms in strict Calvinistic patients differ from those in non-affiliated patients., Method: Seventy depressed adult Dutch nationals receiving treatment as outpatients under the mental health service were asked to fill in a depression self-scoring list (Beck Depression Inventory II (bdi-ii)). A comparison was made between the total scores and scores of symptom clusters of strict Calvinists and the corresponding scores of non-affiliated patients. results The strict Calvinists had a lower total score than the non-affiliated patients on the bdi-ii and their scores were particularly lower for the symptom clusters suicidality and restrictions in functioning., Conclusion: Strict Calvinists differed from the non-affiliated patients in the way in which they presented on a depression self scoring list during depression. Perhaps strict Calvinists have less chance of being diagnosed and treated at an early stage because they conceal their depression and struggle on for a longer time. The study shows that insight into the religious background of Dutch national patients can be important for accurate psychiatric diagnostics.

There is growing evidence that not only the total amount of fat, but also the distribution of body fat determines risks for metabolic and cardiovascular disease. Developmental studies on factors influencing body fat distribution have been hampered by a lack of appropriate techniques for measuring intraabdominal fat in early life. Sonography, which is an established method for assessing abdominal fat distribution in adults, has not yet been evaluated in infants. To adapt the sonographic measurement of abdominal fat distribution to infants and study its reliability. The Generation R study, a population-based prospective cohort study. We included 212 one- and 227 two-year old Dutch infants in the present analysis. Sixty-two infants underwent replicate measurements to assess reproducibility. We developed a standardized protocol to measure the thickness of (1) subcutaneous and (2) preperitoneal fat in the upper abdomen of infants. To this end we defined infancy specific measurement areas to quantify fat thickness. Reproducibility of fat measurements was good to excellent with intraclass correlation coefficients of 0.93-0.97 for intra-observer agreement and of 0.89-0.95 for inter-observer agreement. We observed a pronounced increase in preperitoneal fat thickness in the second year of life while subcutaneous fat thickness increased only slightly, resulting in an altered body fat distribution. Gender did not significantly influence fat distribution in the first two years of life. Our age specific protocol for the sonographic measurement of central subcutaneous and preperitoneal fat is a reproducible method that can be instrumental for investigating fat distribution in early life.

Objective: To study the prevalence and severity of atopic eczema (AE) in children aged 0 to 4 years., Design: Observational study., Methods: We registered all children who visited the child health centres in the West-Veluwe region of the Netherlands between 1 January and 30 April 2005 and used objective criteria to establish if they suffered from AE. Data were also collected about subjective symptoms such as itch and sleeping problems and the severity of AE was established using the Three Item Severity (TIS) score., Results: A total of 9351 children were examined for eczema (5796 infants and 3555 toddlers) . Infants suffered more frequently from eczema than toddlers (8.70% versus 5.54%) and boys suffered more than girls., Conclusion: The total prevalence of AE in this study group of children aged 0 to 4 years was 7.5%.

Aims: To investigate the metabolic consequences of long-term GH treatment in young women with Turner syndrome (TS), several years after GH discontinuation., Methods: Follow-up study of a randomized GH dose-response trial, with 3 GH dosages (1.3, 2.0, and 2.7 mg/m(2)/day). Thirty-nine TS patients (20.0 +/- 2.1 years) participated 4.8 +/- 1.9 years after GH discontinuation. Mean GH treatment duration was 8.7 +/- 2.0 years. Fasting glucose, insulin, and serum lipids were measured., Results: Several years after GH discontinuation, insulin sensitivity remained lower, while beta-cell function and fasting insulin levels remained higher than before treatment. Only BMI influenced beta-cell function. Serum total cholesterol (TC), low-density lipoprotein and high-density lipoprotein (HDL) had further increased compared to 6 months after GH, resulting in higher TC, but also higher HDL levels compared to controls. The atherogenic index remained constant, but lower than controls., Conclusions: Besides height, GH therapy in girls with TS has additional beneficial effects on serum lipids. Nearly 5 years after discontinuation of GH therapy the favorable effect of GH was still noticeable. The GH-induced decrease in insulin sensitivity, however, remained unchanged, possibly due to having TS., (2009 S. Karger AG, Basel)

Aim: To introduce a new floating device for donor corneas to avoid accumulation of debris onto the endothelial surface during organ culture and to facilitate handling of the tissue during preservation and surgery., Methods: From 11 donors, one randomly chosen cornea was stored in organ culture attached to a floating device, while the contralateral cornea was attached to the lid of the phial by a suture ("hanging by suture"). Endothelial cell density (ECD) was evaluated prior to tissue storage and after 2-3 weeks of culture. Furthermore, we compared ECD in a larger group of corneas sent off for transplantation with the device (n = 281) to a historical group of control corneas "hanging by suture" (n = 444)., Results: There was no significant difference in ECD between corneas attached to the floating device or "hanging by suture" (n = 11; p > or = 0.1). Similarly, no different ECDs were observed between corneas sent off for transplantation with the device (n = 281) and the historical group of control corneas "hanging by suture" (n = 444) (p > or = 0.1)., Conclusion: The use of the floating device may not affect tissue quality. Since its introduction, the use of the device has been uneventful and greatly facilitated tissue handling.

Fecal incontinence is a common disorder in children. Many children with fecal incontinence have psychosocial co-morbidity. In this study, the effect of psychosocial co-morbidity on the treatment outcome of children with fecal incontinence was evaluated. One hundred and fifty children with fecal incontinence were treated in a multidisciplinary program. All children had been treated unsuccessfully for at least one year before entering the program. The treatment consisted of laxative treatment, psychosocial interventions, and biofeedback training. Psychosocial co-morbidity was classified according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV). One hundred and forty-one children were completely analyzed (102 boys, mean age 9.6 (range 6.5-16.5) years). Of these, 31 (22%) children had fecal incontinence without constipation and 110 (78%) children had fecal incontinence associated with constipation. In 95% of children, at least one psychosocial co-morbidity was present. Treatment was successful at 12 months in 69% of patients. Treatment was less successful in children with attention deficit hyperactivity disorder (ADHD), in children with parent-child relational problems, and in mentally retarded children. The results indicate that the early assessment and treatment of psychosocial co-morbidity might improve treatment response in children with fecal incontinence. Children with fecal incontinence are treated less successfully in the first year if they have ADHD, parent-child relational problems, or mental retardation. Psychosocial evaluation and the early assessment and treatment of psychosocial co-morbidity is indicated in order to improve response rate. Family counseling--aimed at improving parent-child relations--should be an integral part of a multidisciplinary treatment program for fecal incontinence.

Aim: Recent phylogenetic analyses on the herpes simplex virus type 1 (HSV-1) genes US4, encoding glycoprotein G (gG) and US7, encoding gI, of clinical HSV-1 isolates have led to the classification of HSV-1 into three genotypes, arbitrarily designated as A, B and C. The prevalence of the HSV-1 gG and gI genotypes and their potential disease association was determined in a large cohort of patients with herpetic keratitis (HK)., Methods: Primary corneal HSV-1 isolates of 178 HK patients were genotyped by a PCR-based restriction fragment length polymorphism method targeting the viral genes US4 and US7., Results: Genotype B was more frequently expressed by the corneal HSV-1 isolates compared with genotypes A and C. Fifty-five of 178 corneal isolates (31%) had different genotypes in both loci. No clinically relevant associations were observed between the HSV-1 genotypes and disease outcome in the HK patients studied., Conclusions: The data presented demonstrate a high frequency of recombinant corneal HSV-1 isolates and suggest that clinical outcome of HSV-1-induced keratitis is independent of a gG or gI genotype.

Objective: To compare effects on premature infants' weight gain of a computer-generated and a nurse-determined incubator humidity strategy. An optimal humidity protocol is thought to reduce time to regain birthweight., Design: Prospective randomized controlled design., Setting: Level IIIC neonatal intensive care unit in the Netherlands., Participants: Infants of 24 to 30 weeks gestational age with a birthweight less than 1,500 g., Intervention: Two incubator humidity strategies were studied: computer-generated and nurse-determined humidity., Main Outcome Measure: Time needed to regain birthweight., Results: One hundred thirty six infants were enrolled: 65 were exposed to the computer-generated strategy and 71 to the nurse-determined strategy. Demographic characteristics were well balanced between groups, with birthweight 981 +/- 245 versus 991 +/- 213 g, mean gestational age 27.7 +/- 1.7 versus 27.7 +/- 1.6 weeks. Main outcome did not significantly differ between strategies: survival analysis showed an equal number of days needed to regain birthweight (median 9 days, with 95% CIs 8-10 and 7-11 for infants exposed to the computer-generated and nurse-determined humidity strategy, respectively)., Conclusion: Computer-generated strategy does not reduce the time needed to regain birthweight.

What Is Already Known About This Subject: The influence of CYP2C19 on the kinetics and dynamics of omeprazole, lansoprazole and rabeprazole has been studied in Japanese subjects. * It has been suggested that subjects with *1/*1 genotype might need stronger acid suppression than *1/*2 and *2/*2 subjects. This suggestion comes from data in Japanese subjects and has not been confirmed in Caucasians. * Furthermore, a novel CYP2C19 mutation, *17, which mainly occurs in Caucasians has been discovered. This mutation has been associated with clinical failure, but its relevance for therapy with PPIs has not been studied yet., What This Study Adds: In this study, the influence of CYP2C19 on both the pharmacokinetics and dynamics in Caucasian subjects after single and repeated dosing has been investigated. * This is the first study showing that Caucasian subjects with *1/*1 and *1/*17 mutations need stronger acid-inhibition. In this study three proton pump inhibitors (omeprazole, lansoprazole and pantoprazole, in different doses) were studied of which pantoprazole had not been studied before in this setting, not even in Japanese., Aims: To investigate the impact of CYP2C19 mutations *2-*6 and *17 on acid-inhibition and pharmacokinetics of lansoprazole (L15), omeprazole (O10, O20) and pantoprazole (P40) in Caucasians., Methods: CYP2C19 genotyping for *2-*6 and *17 mutations was assessed in subjects who were H. pylori negative in two randomized crossover trials. The influence of CYP2C19 mutations on single and repeated administration of L15 and O10 (study A) and O20 and P40 (study B) was investigated. Pharmacokinetics and the cumulative percentage of time with intragastric pH above 4 (% > pH 4) were assessed on day 1 and 6., Results: For study A CYP2C19 genotyping found five *1/*1, four *1/*2, one *1/*17 and one *2/*17. For study B the results were six *1/*1, two *1/*2, six *1/*17, one *2/*2 and one *2/*17. For all PPIs AUC was highest in *2/*2 and lowest in *1/*17. On day 1, all PPIs significantly increased percentage >pH 4 compared with baseline. *1/*1 genotype showed no significant acid-inhibition after L15, O10 and O20. *1/*17 genotype showed no significant acid-inhibition after O20 and P40. *1/*2 genotype showed significant acid-inhibition after L15 and O10. On day 6, all four PPIs showed significantly increased acid-inhibition. *1/*1 and *1/*17 showed a significantly increased percentage > pH 4 after treatment with O20 and P40. However, in *1/*1 subjects percentage > pH 4 was not significantly increased after L15 and O10. *1/*2 genotype showed a significant acid-inhibitory effect after repeated dosing with L15 and O10., Conclusions: Caucasian subjects with *1/*1 and *1/*17 genotype need stronger acid-suppression therapy, especially during the first days of treatment or with on-demand therapy.

Unlabelled: Outcome reporting of intra-articular calcaneal fractures is inconsistent. This study aimed to identify the most cited outcome scores in the literature and to analyze their reliability and validity. A systematic literature search identified 34 different outcome scores. The most cited outcome score was the American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot score, followed by the Maryland Foot Score (MFS) and the Creighton-Nebraska score (CN). Reliability (internal consistency) and validity (content, construct, and criterion) were determined for the 3 outcome scoring systems. Internal consistency (Cronbach's alpha, reliability) was similar for the Maryland Foot Score (alpha=0.82) and American Orthopedic Foot and Ankle Society hindfoot score (alpha=0.78), but lower for the Creighton-Nebraska (alpha = 0.61). Floor and ceiling effects were good for all 3 scores. The individual items within these outcome scores showing best content validity were pain, return to work, subtalar range of motion, walking distance, ankle range of motion, and gait abnormalities or limping. Construct validity was good for all individual items except sagittal motion, stability at physical exam, and shoe size. The 3 outcome scores showed high correlation with patient satisfaction as measured with a visual analog scale (VAS, criterion validity) and indication for an arthrodesis. In conclusion, pending consensus, we would recommend choosing between the widely accepted, reliable and valid AOFAS hindfoot and the Maryland Foot Score as the scoring systems of choice., Level of Clinical Evidence: 2.

Objective: To assess the intra- and interobserver reproducibility of fetal biometry measurements by transabdominal ultrasound in early pregnancy., Methods: The study consisted of 21 singleton pregnancies with a gestational age between 9 and 14 weeks. Intraclass correlation coefficients (ICCs) and coefficients of variation (CVs) were calculated. Bland and Altman plots were computed to analyze agreement for measurements between and among observers. Limits of agreement +/- 2 SD for the differences in fetal biometry measurements in proportions of the mean of the measurements were derived., Results: High intra- and interobserver ICCs were found, ranging from 0.998, crown-rump length (CRL) to 0.982, femur length (FL) and CVs ranging from 1.4% (CRL) to 5.9% (FL). Limits of agreement in the Bland and Altman plots ranged from - 2.7 to 2.3% (CRL) difference from the mean to - 13 to 23% (FL) difference. Agreement for fetal biometry increased with fetal size., Conclusions: This study demonstrated good reproducibility of most measurements of fetal biometry in early pregnancy by abdominal ultrasound. CRL and biparietal diameter (BPD) showed high reproducibility and agreement, and head circumference (HC) to a lesser extend, from 9 weeks of gestational age onwards. abdominal circumference (AC) is only reliable from circa 11 weeks onwards. FL has a poor reproducibility before 14 weeks of gestational age., (Copyright (c) 2008 John Wiley & Sons, Ltd.)

Objective: To report endothelial cell densities (ECDs) and their correlation to anterior chamber depth (ACD) after implantation of the Artisan intraocular phakic lens., Design: Prospective observational case series., Participants: Three hundred eighteen eyes of 173 myopic patients treated with the Artisan iris-fixated phakic intraocular lens (IOL)., Methods: Eyes with an ACD ranging between 2.89 and 4.5 mm were implanted with the Artisan phakic IOL. Endothelial cell density measurements were performed preoperatively and at each follow-up examination using a noncontact specular microscope., Main Outcome Measures: Endothelial cell density (cells per square millimeter)., Results: Follow-up ranged between 1 (82 eyes) and 7 years (13 eyes) (mean, 35.3+/-20.7 [standard deviation] months per eye). After 3 years, there was a significant loss in ECD (P< or =0.03). At 5 years, mean observed endothelial cell loss was 8.3% (5.3% corrected for a natural endothelial cell loss of 0.6% a year). Endothelial cell density loss remained progressive throughout our follow-up period. After 3 years, a significant negative correlation between ACD and endothelial cell loss was revealed (P< or =0.03). Patient age, gender, refractive error, incision size, and side of the eye were not correlated to ECD loss. All corneas remained clear throughout the study., Conclusion: After 3 years, a significant ECD loss was revealed. This ECD loss was significantly negatively correlated to the ACD. We therefore suggest that eyes just meeting the minimum ECD requirement have greater ACDs to compensate for possible greater endothelial cell loss and that patients with shallow anterior chambers have higher ECDs. Artisan phakic lens implantation in young eyes narrowly meeting the minimum criteria of endothelial cell density (2,000 cells/mm(2)) and ACD (2.6 mm) should perhaps be reevaluated, due to longer exposure to higher rates of endothelial cell loss.

The purpose of the present study is to compare the efficacy of imipramine in the treatment of psychotic versus nonpsychotic depression. Previous studies report varying results of monotherapy with antidepressants in psychotic depression. Because psychotic depression is seriously underinvestigated, performing a post hoc analysis of randomized clinical trials consisting of both psychotic and nonpsychotic depressed patients may contribute to the discussion on the optimal treatment of depressed patients with mood-congruent psychotic features. A total of 112 patients diagnosed with major depression (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) (40 with psychotic depression and 82 without psychotic features) received treatment with imipramine for 6 weeks after a washout period of 7 days. Imipramine doses were adjusted to attain a predefined fixed plasma level. Treatment response was assessed with the Hamilton Rating Scale for Depression (HAM-D). A logistic regression analysis showed a significantly larger reduction in HAM-D score in the sample with psychotic features compared with the nonpsychotic sample (regression coefficient, -3.47; SE, 1.7; P = 0.04). According to the primary outcome criterion, that is, the change in HAM-D score, imipramine was significantly more effective in the sample with psychotic depression compared with the nonpsychotic depressed patients. The contradiction between our results and those of several previous studies may be due to the fixed plasma level dosing of imipramine refraining from concurrent psychotropic medication or limiting our patient sample to patients with mood-congruent psychotic features.

Context: Low birth weight is associated with increased risks for adult cardiovascular disease (CVD) and diabetes mellitus type 2 (DM2). Adiponectin and resistin are hormones, considered, respectively, protective and disadvantageous regarding these risks. No data exist on the effect of long-term GH treatment on these hormones and inflammatory markers in children born small for gestational age (SGA)., Objective: To describe longitudinal changes in inflammatory markers and adipocytokines during and after a long-term dose-response GH study., Design: Longitudinal dose-response study [group A: 1 mg/m(2) body surface area (BSA) (approximately 0.033 mg/kg/day) vs. group B: 2 mg/m(2) BSA (approximately 0.067 mg/kg/day)] and comparison with age-related controls., Patients: One hundred and three SGA children., Measurements: We measured adiponectin, resistin, interleukin-6 (IL-6) and C-reactive protein (CRP) levels at baseline, after 1 and 7 years of GH treatment and 6 months after discontinuation of GH., Results: Adiponectin levels decreased over time, but remained comparable with controls. Resistin levels increased and remained lower or comparable with controls. There were no significant differences between the GH dosage groups. After the GH treatment was stopped, adiponectin was decreased in group B and resistin increased in group A. GH therapy did not affect IL-6 and CRP levels at any time point. An increase in body mass index (BMI) standard deviation score (SDS) over time was associated with a decrease in adiponectin levels. None of the markers were associated with insulin sensitivity., Conclusions: Long-term GH treatment is not associated with disadvantageous changes in adiponectin, resistin, IL-6 and CRP levels, neither during nor after GH treatment.

Introduction: A limitation of pre-hospital monitoring is that vital signs often do not change until a patient is in a critical stage. Blood lactate levels are suggested as a more sensitive parameter to evaluate a patient's condition. The aim of this pilot study was to find presumptive evidence for a relation between pre-hospital lactate levels and in-hospital mortality, corrected for vital sign abnormalities., Methods: In this prospective observational study (n = 124), patients who required urgent ambulance dispatching and had a systolic blood pressure below 100 mmHg, a respiratory rate less than 10 or more than 29 breaths/minute, or a Glasgow Coma Scale (GCS) below 14 were enrolled. Nurses from Emergency Medical Services measured capillary or venous lactate levels using a hand-held device on arrival at the scene (T1) and just before or on arrival at the emergency department (T2). The primary outcome measured was in-hospital mortality., Results: The average (standard deviation) time from T1 to T2 was 27 (10) minutes. Non-survivors (n = 32, 26%) had significantly higher lactate levels than survivors at T1 (5.3 vs 3.7 mmol/L) and at T2 (5.4 vs 3.2 mmol/L). Mortality was significantly higher in patients with lactate levels of 3.5 mmol/L or higher compared with those with lactate levels below 3.5 mmol/L (T1: 41 vs 12% and T2: 47 vs 15%). Also in the absence of hypotension, mortality was higher in those with higher lactate levels. In a multivariable Cox proportional hazard analysis including systolic blood pressure, heart rate, GCS (all at T1) and delta lactate level (from T1 to T2), only delta lactate level (hazard ratio (HR) = 0.20, 95% confidence interval (CI) = 0.05 to 0.76, p = 0.018) and GCS (HR = 0.93, 95% CI = 0.88 to 0.99, p = 0.022) were significant independent predictors of in-hospital mortality., Conclusions: In a cohort of patients that required urgent ambulance dispatching, pre-hospital blood lactate levels were associated with in-hospital mortality and provided prognostic information superior to that provided by the patient's vital signs. There is potential for early detection of occult shock and pre-hospital resuscitation guided by lactate measurement. However, external validation is required before widespread implementation of lactate measurement in the out-of-hospital setting.

Background: When patients with cardiovascular disorders undergo electroconvulsive therapy (ect) they sometimes have to be treated for tachycardia and high blood pressure., Aim: To describe the effects of beta-blockers on seizure duration and cardiovascular variables in patients undergoing ect., Method: Search for studies in Medline, with the keywords 'beta-adrenergic blocking agents' and 'electroconvulsive therapy'. Only articles based on randomised placebo-controlled investigations were included. results The search strategy produced 21 articles. These were assessed by all authors. Esmolol was the drug administered in most of the trials. Since seizure duration can influence the therapeutic effect of ect it is advisable to use bilateral electrode placement in patients with cardiovascular risk factors and to administer esmolol prior to seizure induction., Conclusion: The beta-blocker of choice for use during ect seems to be esmolol; it can shorten seizure duration, although the effect is probably dose-dependent. Esmolol is also the drug of choice in ect sessions for patients without cardiovascular risk factors but who develop prolonged hypertension or tachycardia. A possible alternative is labetalol, but its longer half-life is a disadvantage, particularly if it is administered in a high dose. So far, experience with landiolol is limited, but its short half-life, greater cardioselectivity and higher potency mean that it could be a promising alternative.

Objective: The purpose of this study was to investigate the interobserver variability and the test-retest variability of the Dysphonia Severity Index (DSI), a multiparametric instrument to assess voice quality., Methods: The DSI was measured in 30 nonsmoking volunteers without voice complaints or voice disorders by two speech pathologists. The subjects were measured on 3 different days, with an interval of 1 week., Results: The difference in DSI between two observers (interobserver difference) was not significant. The intraclass correlation coefficient for the DSI was 0.79. The standard deviation of the difference between two duplicate measurements by different observers was 1.27., Conclusion: Differences in measurements between different observers were not significant. The intraclass correlation coefficient of the DSI was 0.79, which is to be considered good. Differences in DSI within one patient need to be larger than 2.49 to be significant., (Copyright 2008 S. Karger AG, Basel.)

Background: Therapy with inhaled corticosteroids (ICS) is beneficial in patients with asthma. However, in preschool children with symptoms like cough, wheeze, or shortness of breath diagnosing asthma is difficult. Therefore, the role of ICS in the management of preschool children with recurrent respiratory symptoms is unclear. We assessed the effectiveness of ICS in preschool children with recurrent respiratory symptoms in general practice., Methods: In this multicenter, randomized, double blind, placebo controlled trial, 96 children aged 1-5 years consulting their general practitioners for recurrent respiratory symptoms and in whom treatment with ICS was considered by the general practitioner were randomly allocated to receive ICS (fluticasone propionate 200 mcg/day by metered dose inhaler/spacer combination) or placebo for 6 months. Outcome assessments were carried out 1, 3, and 6 months after randomization. The primary outcome measure was the symptom score (cough, shortness of breath and wheeze during day and night) as measured by a symptom diary card. Secondary endpoints were symptom-free days, use of rescue medication, adverse events, and lung function variables as measured by the interrupter technique and forced oscillation technique., Results: During the 6 months treatment period, symptoms improved in both groups, with no differences between ICS and placebo. In addition, none of the secondary outcome parameters showed differences between both treatment groups., Conclusion: ICS treatment has no beneficial effect in preschool children with recurrent respiratory symptoms in general practice. We therefore recommend a watchful waiting policy with only symptomatic treatment in these children. General practitioners and pediatricians should be aware of the high probability of overtreatment when prescribing ICS in these children.

About 4-10% of children and adolescents suffer from migraine. In the last few years, several studies have been performed to assess the efficacy and safety of triptans for the acute treatment of migraine in children and adolescents. Only sumatriptan nasal spray has been approved for the treatment of acute migraine with or without aura in adolescents aged 12-17 years in Europe. This review describes the results of the studies with sumatriptan nasal spray that have been performed in children and adolescents, including a study performed in the Netherlands.

Purpose: To report endothelial cell density (ECD) after posterior lamellar keratoplasty (PLK)., Design: Prospective, interventional case series., Methods: In a single institution, PLK was performed in 15 eyes of 15 patients with pseudophakic bullous keratopathy (PPBK), Fuchs endothelial dystrophy (FED), or both. In 11 eyes, the donor tissue was inserted unfolded through a 9.0-mm sclerocorneal incision. In four eyes, the donor was folded and inserted through a 5.0-mm incision. The ECD measurements were performed in each patient at regular intervals until three years after surgery, and then in all patients simultaneously at 54 to 84 months after surgery., Results: Three patients were not available for follow-up. One graft had decompensated. In the remaining 11 eyes, ECDs ranged from 368 to 1576 cells/mm(2). Monophasic and biphasic regression models of ECD against time were fitted for each technique separately., Conclusions: After PLK, ECD declined at a high rate. Both early- and longer-term loss rates may be related to surgical technique.

Objectives: This long-term prospective study focuses on the effects of electroconvulsive therapy (ECT) on everyday memory function and on semantic memory function., Methods: Results of memory test from 96 consecutive inpatients treated for unipolar depression were analyzed prospectively before ECT, after ECT treatment, and at 3- and 12-month follow-up. Everyday memory function was assessed by means of the Rivermead Behavioural Memory Test (RBMT) and semantic memory by 2 forms of the word fluency test., Results: In our study, age had a constant and significant negative effect on everyday memory (RBMT score) over time. Bilateral electrode placement mainly influenced everyday memory, which was significantly improved at 3-month follow-up. One year after discharge, the RBMT scores were not significantly different from pretreatment levels, indicating that ECT does not affect everyday memory on the longer term. Scores on both word fluency tests for semantic memory were significantly influenced by age over time. The effect of age changed from a negative influence directly after ECT to a positive effect at follow-up. This advantage of higher age indicates that the semantic memory of older patients receiving ECT for severe mood disorder shows greater improvement at follow-up compared with younger patients. Over time, the scores on only 1 of the word fluency tests were significantly influenced by mainly bilateral electrode placement., Conclusions: A small but reversible decrease in everyday memory occurs after ECT in depressed patients, which is influenced by age and electrode placement. Semantic memory shows a fluctuating but recovering course, which is also influenced by age and electrode placement. During follow-up, the improvement in semantic memory was greater in the older patients.

Objective: The aim of this study was to correlate the functional outcome after treatment for displaced intra-articular calcaneal fracture with plain radiography., Design: The design was a prognostic study of a retrospective cohort with concurrent follow-up., Patients: A total of 33 patients with a unilateral calcaneal fracture and a minimum follow-up of 13 months participated. Patients filled in three disease-specific questionnaires, graded their satisfaction and the indication for an arthrodesis was noted. Standardised radiographs were made of the previously injured side and the normal (control) side. Different angles and distances were measured on these radiographs and compared with values described in the literature. The differences in values in angles and distances between the injured and uninjured (control) foot were correlated with the outcome of the questionnaires, and the indication for an arthrodesis., Results: None of the angles correlated with the disease-specific outcome scores. Of the angles only the tibiotalar angle correlated with the VAS (r = 0.35, p = 0.045) and only the absolute foot height correlated with the indication for an arthrodesis (odds = 0.70, CI = 0.50-0.99)., Conclusion: In this study the radiographic evaluation correlated poorly with the final outcome. Measurements on plain radiographs seem not to be useful in determining outcome after intra-articular calcaneal fractures.

Context: IGF-I plays an important role in pre- and postnatal growth. Its serum levels are regulated by metabolic and genetic factors. Mean total IGF-I in short, small for gestational age (SGA) children is reduced, but within the normal range. Free/dissociable IGF-I is the bioactive form of IGF-I., Objectives: The aim of the study was to investigate changes in free IGF-I during GH treatment in short SGA children and to evaluate whether free IGF-I levels contribute to predicting first-year growth response and/or adult height. DESIGN, SETTING, AND INTERVENTION: We conducted a randomized, double-blind GH dose-response study with a GH dose of either 1 mg/m(2).d (group A) or 2 mg/m(2).d (group B). Free IGF-I, total IGF-I, and IGF binding protein (IGFBP)-3 were determined at baseline, after 1 and 5 yr, at stop, and 6 months after GH discontinuation., Patients: We studied 73 (46 male) short SGA children (36 group A) with a baseline mean age of 7.7 (2.2) yr and a mean GH duration of 8.2 (2.1) yr., Main Outcome Measures: Untreated SGA children had a mean free IGF-I sd score (SDS) of -0.2 (1.2), not related to total IGF-I. During GH therapy, free IGF-I significantly increased to 1.6 (0.7) SDS, as did total IGF-I and IGFBP-3 [2.0 (0.8) and 1.3 (0.9), respectively]. Multiple regression analysis showed that baseline free IGF-I and IGFBP-3 were negatively correlated with adult height SDS, whereas baseline bone age delay, target height SDS, baseline height SDS, and GH dose were positively correlated. Free IGF-I was also negatively correlated with first-year growth response., Conclusions: Circulating baseline free IGF-I and IGFBP-3 were better predictors for adult height in GH-treated SGA children than total IGF-I, or total IGF-I to IGFBP-3 ratio. This suggests a possible role for free IGF-I measurement in predicting the effect of GH therapy in short SGA children.