Treating benign ureteroenteric strictures: 27-year experience comparing endourological techniques with open surgical approach.

PURPOSE: To compare open surgical anastomotic revision with endourological techniques for the treatment of ureteroenteric strictures in patients with urinary diversions. METHODS: All records of patients treated for ureteroenteric strictures in our clinic between 1989 and 2016 were retrospectively reviewed. In 76 patients, 161 completed procedures were analyzed: 26 open revisions vs. 135 endourological treatments, including balloon dilation, Wallstent and/or laser vaporization. RESULTS: Median follow-up was 34 months. At 60 months, patency rates were 69% (95% CI 52-92%) after open vs. 27% (95% CI 19-39%) after endo-treatment (p = 0.003); median patency duration was 15.5 vs. 5 months, respectively (p = 0.014). Eventually, 15% of patients required open surgery after primary endo-treatment and 21% received endoscopic re-treatment after primary open surgery. Cox regression analysis revealed no confounding factors among the risk factors added to the model. Complication rates were higher after open surgery (27% Clavien 2, 12% Clavien 3-4 vs. 5% Clavien 1-2, 3% Clavien 3, p = 0.528). Median postoperative hospital stay was 14 days (open) vs. 2 days (endo), p < 0.001. Mean estimated glomerular filtration rate improved with + 17 (open) vs. + 8.1 (endo), p = 0.024. Renal function was compromised in 8% of patients in the open surgery group vs. 6% in the endo-treatment group. CONCLUSIONS: In these patients, in terms of patency and patency duration, open surgery was superior to endourology. Nevertheless, endourological treatments offer a safe and less-invasive alternative to delay or avoid open surgery, especially in patients who are unfit for open surgery.

Effect of estradiol on the expression of renal sodium transporters in rats.

BACKGROUND: Although estradiol has been thought to perform an important role in blood pressure regulation, the effects of estradiol on the expression of renal sodium transporters are not fully understood. METHODS: Female Sprague-Dawley rats were treated with 17ß-estradiol or vehicle for 10 days after ovariectomy, and after both ovariectomy and adrenalectomy to eliminate the effect of aldosterone. RESULTS: In the ovariectomized (OVX) rats, estradiol decreased the abundance of the Na-K-2Cl cotransporter (NKCC2) (31.5% of control (OVX), p < 0.01), Na-Cl cotransporter (NCC) proteins (40.5% of control (OVX), p < 0.01) and α- and γ-subunits of the epithelial sodium channel (ENaC) (44.7% and 11.0% of control (OVX), p < 0.01). Estradiol also reduced plasma aldosterone levels (OVX + 17ß-estradiol vs. OVX, 116.3 ± 44.4 vs. 184.2 ± 33.4 pmol/l, p < 0.05) and systolic blood pressure (OVX + 17ß-estradiol vs. OVX, 115 ± 4 vs. 132 ± 2 mmHg, p < 0.05). In rats having undergone adrenalectomy and ovariectomy, estradiol did not reduce systolic blood pressure, or the expression of sodium transporters. CONCLUSION: Estradiol decreased systolic blood pressure, plasma aldosterone levels, and the expression of renal sodium transporters. After aldosterone was eliminated, estradiol did not affect blood pressure or the expression of sodium transporters, which indicates that the effect of estradiol on the renal sodium transporters is at least partly influenced by aldosterone.

MR compatibility, safety and accuracy of the redesigned UMC Utrecht single needle implant device.

Purpose. The Utrecht single needle implant device (SNID) was redesigned to increase needle insertion velocity. The purpose of this study is to evaluate the magnetic resonance compatibility, safety and accuracy of the implant device preparing its application in a patient study to investigate the feasibility of inserting a brachytherapy needle into the prostate to a defined tumor target point.Methods. Several experiments were performed to evaluate the mechanical and radiofrequency safety of the needle system, the magnetic field perturbation, the calibration of the implant device in the MR coordinate system, functioning of the implant device during imaging and accuracy of needle insertion.Results. Endurance experiments showed the mechanical safety of the needle system. Magnetic field perturbation was acceptable with induced image distortions smaller than 0.5 mm for clinical MR sequences. Calibration of the implant device in the MR coordinate system was reproducible with average error (mean±standard deviation) of 0.2 ± 0.4 mm, 0.1 ± 0.3 mm and 0.6 ± 0.6 mm in thex,y- andz- direction, respectively. The RF safety measurement showed for clinical MR imaging sequences maximum temperature rises of 0.2 °C at the entry and tip points of the needle. Simultaneous functioning of the implant device and imaging is possible albeit with some intensity band artifacts in the fast field echo images. Finally, phantom measurements showed deviations amounting 2.5-3.6 mm measured as target-to-needle distance at a depth of 12 cm.Conclusions. This preclinical evaluation showed that the MR compatibility, safety and accuracy of the redesigned UMC Utrecht SNID allow its application in a patient study on the feasibility of inserting a brachytherapy needle into the prostate to a defined tumor target point.

Depression and health-related quality of life in maintenance hemodialysis patients.

BACKGROUND: This study was designed to determine the prevalence of depression among hemodialysis (HD) patients from urban hospitals in Korea, to illustrate demographic factors and biomarkers associated with depression and health-related quality of life (HRQOL), and to demonstrate association between depression and HRQOL. PATIENTS AND METHODS: For this multicenter, cross-sectional study, 160 HD patients from 3 university teaching hospitals and 3 local dialysis units in Korea were enrolled. Korean Beck's depression inventory and Korean version of Kidney Disease Quality of Life short form, version 1.3 (KDQOL-SFTM 1.3) were used to evaluate depression and quality of life, respectively. RESULTS: Depression was found in 51 out of 160 (31.9%) patients. Old age (> 60 years old), low hemoglobin level (< 10 g/dl), and low economic status were associated with depression, and old age (OR 6.138, p = 0.001) was the most important risk factor among them. Old age, female gender, presence of diabetes mellitus, high comorbidity index score (modified Charlson comorbidity index > or = 6), hypoalbuminemia (< 4.0 g/dl), and high CRP (> 0.5 mg/dl) were common factors associated with decreased HRQOL. Depression and HRQOL showed inverse linear relationship. CONCLUSIONS: Moderate to severe depression was common in maintenance HD patients in Korea. Among factors associated with depression and decreased HRQOL, some characteristics are potentially modifiable by social and medical intervention. Further prospective studies are warranted to see whether depression and HRQOL can be improved by modifying these factors.

Egr-1 mediates transcriptional activation of IGF-II gene in response to hypoxia.

We have previously reported that the exposure of human HepG2 cells to hypoxic conditions results in the overexpression of human insulin-like growth factor II (IGF-II) mRNA whose size is 6.0 kb. This particular size of IGF-II mRNA is transcribed under the control of the IGF-II P3 promoter. In the present study, to delineate the molecular mechanism for the activation of the IGF-II gene, we examined the induction of P3 promoter activity in HepG2 cells by hypoxia in the transient expression system. In this system, hypoxia induced a linear increase within 24 h in the expression of luciferase that was driven by the IGF-II P3 promoter. To further delineate which factors mediate this response, the expression pattern of regulators of the P3 promoter, Egr-1, Sp1, and WT1, were analyzed by reverse transcription-PCR and Northern blot analysis. We found that hypoxia increased the expression of Egr-1 but not of Sp1. In contrast, the level of WT1, a repressor of IGF-II expression, was markedly decreased during hypoxia. The mRNA stability assay revealed that the induction of transcription is the mechanism of underlying Egr-1 mRNA elevation. We then investigated the effects of hypoxia on the DNA binding activity of Egr-1. Both electrophoretic mobility shift assay and supershift assay demonstrated that the DNA binding activity of the Egr-1 protein was increased by hypoxia. In addition, the level of Egr-1 protein was also increased under the hypoxia as determined by Western blot analysis. Cotransfection of HepG2 cells with an Egr-1 expression vector and an IGF-II P3 promoter-luciferase reporter plasmid showed that the transcription of IGF-II was activated by Egr-1 in a dose-dependent manner. Moreover, the elevation of IGF-II P3 promoter activity was induced synergistically by the cotreatment of hypoxia with Egr-1 overexpression. Deletion of sequences in the IGF-II P3 promoter containing Egr-1 binding sites did not respond to hypoxic stress. Taken together, these data strongly indicate that hypoxia-induced IGF-II expression in HepG2 cells is due to the enhanced activity of Egr-1 on the IGF-II P3 promoter and that the Egr-1 binding site in the IGF-II P3 promoter is essential for the transcriptional regulation of IGF-II under hypoxic conditions.

Mitofusins deficiency elicits mitochondrial metabolic reprogramming to pluripotency.

Cell reprogramming technology has allowed the in vitro control of cell fate transition, thus allowing for the generation of highly desired cell types to recapitulate in vivo developmental processes and architectures. However, the precise molecular mechanisms underlying the reprogramming process remain to be defined. Here, we show that depleting p53 and p21, which are barriers to reprogramming, yields a high reprogramming efficiency. Deletion of these factors results in a distinct mitochondrial background with low expression of oxidative phosphorylation subunits and mitochondrial fusion proteins, including mitofusin 1 and 2 (Mfn1/2). Importantly, Mfn1/2 depletion reciprocally inhibits the p53-p21 pathway and promotes both the conversion of somatic cells to a pluripotent state and the maintenance of pluripotency. Mfn1/2 depletion facilitates the glycolytic metabolic transition through the activation of the Ras-Raf and hypoxia-inducible factor 1α (HIF1α) signaling at an early stage of reprogramming. HIF1α is required for increased glycolysis and reprogramming by Mfn1/2 depletion. Taken together, these results demonstrate that Mfn1/2 constitutes a new barrier to reprogramming, and that Mfn1/2 ablation facilitates the induction of pluripotency through the restructuring of mitochondrial dynamics and bioenergetics.

Are autoimmune thyroid dysfunction and depression related?

The objective of this study was to examine the relationship between autoimmune thyroid disease and depression in perimenopausal women. Thyroid function [TSH, free T4, and thyroid peroxidase antibodies (TPO-Ab)] and depression (using the Edinburgh Depression Scale) were assessed cross-sectionally together with other determinants of depression. The subjects were 583 randomly selected perimenopausal women (aged 47-54 yr) from a community cohort of 6846 women. The main outcome measures were the occurrence of thyroid dysfunction (abnormal free T4 and/or TSH or elevated levels of TPO-Ab) and the concomitant presence of depression according to the Edinburgh Depression Scale. Neither biochemical thyroid dysfunction nor menopausal status was related to depression. Apart from several psycho-social determinants (the occurrence of a major life event, a previous episode of depression, or financial problems), an elevated level of TPO-Ab (> or = 100 U/mL) was significantly associated with depression (odds ratio, 3.0, 95% confidence interval, 1.3-6.8). We conclude that women with elevated TPO-Ab levels are especially vulnerable to depression, whereas postmenopausal status does not increase the risk of depression.

The diagnostic value of sural nerve T cells in chronic inflammatory demyelinating polyneuropathy.

BACKGROUND: T-cell infiltrates in sural nerve biopsy specimens of patients with inflammatory neuropathies have been reported, suggesting a role for T cells in the pathogenesis, but the specificity of the presence and localization of sural nerve T cells in chronic inflammatory demyelinating polyneuropathy (CIDP) is unknown. OBJECTIVE: To study the diagnostic value of the number and distribution of sural nerve T cells in CIDP. METHODS: We performed a quantitative immunohistochemical examination of T cells in sural nerve biopsy specimens taken from 23 patients with a CIDP and compared them with sural nerves of 15 patients with a chronic idiopathic axonal polyneuropathy (CIAP), 5 patients with a vasculitic neuropathy, and 10 normal controls. RESULTS: T cells were found in sural nerves of all CIDP patients as well as in all disease and normal controls. Only six CIDP patients had increased numbers and densities of T cells compared with CIAP patients and controls. Based on the distribution of endoneurial or epineurial T cells, it was not possible to differentiate CIDP patients from CIAP patients or normal controls. In patients and controls perivascular epineurial T cells predominated. Increased numbers and densities of sural nerve T cells in patients with CIDP were associated with female sex, a more severe disease course, worse outcome, highly elevated CSF protein level, and a larger sural nerve area, but not with loss of myelinated nerve fibers in the sural nerve biopsy sample or demyelinating features on electrophysiologic examination. CONCLUSIONS: In the majority of CIDP patients, the number and distribution of T cells in sural nerve biopsy samples were similar to patients with noninflammatory neuropathies and normal controls. Only large numbers of sural nerve T cells are specific for inflammatory neuropathies and therefore of diagnostic value for CIDP.

Thyroid peroxidase antibodies during gestation are a marker for subsequent depression postpartum.

OBJECTIVE: Depression is not adequately diagnosed in many cases. Therefore, the question arises as to whether markers exist for depression. We investigated whether the presence of thyroperoxidase antibodies (TPOAbs) during pregnancy can be regarded as a marker for depression in the first year postpartum, particularly in relation to (overt or subclinical) thyroid dysfunction and other determinants of depression. DESIGN: This work was a prospective observational study. PATIENTS: A cohort of 310 unselected women (residing in the Kempen Region, southeastern Netherlands) were visited at 12 and 32 weeks gestation and at 4, 12, 20, 28 and 36 weeks postpartum. METHODS: At each visit, TSH, free thyroxine and TPOAb testing was performed, determinants associated with depression were asked for, and depression was assessed (according to the Research Diagnostic Criteria). Multiple logistic regression was performed to determine independent risk factors (odds ratios, ORs) for depression in gestation and/or postpartum depression. RESULTS: Data for 291 women were available for analysis; 41 women (14.1%) had TPOAbs at one or more time points, and 117 women (40.1%) had depression at one or more time points postpartum. The multiple logistic regression analysis showed that TPOAbs were independently associated with depression at 12 weeks gestation and at 4 and 12 weeks postpartum (OR, 95% confidence interval: 2.4 (1.1-6.0), 3.8 (1.3-7.3) and 3.6 (1.2-7.1) respectively). After the exclusion of women who were depressed at 12 weeks gestation (n=70), the presence of TPOAbs during early pregnancy was still found to be associated with the development of postpartum depression (OR, 95% confidence interval: 2.8 (1.7-4.5); after exclusion of women who had had depression in earlier life (n=51), TPOAb during early gestation was still associated with postpartum depression (OR, 95% confidence interval: 2.9 (1.8-4.3). CONCLUSIONS: The presence of TPOAbs during gestation is associated with the occurrence of subsequent depression during the postpartum period and as such can be regarded as a marker for depression.

Characteristics of the Edinburgh Post Natal Depression Scale in The Netherlands.

The Edinburgh Post Natal Depression Scale (EPDS), a 10-item self-rating depression scale, was translated into Dutch and compared in 293 postpartum women with other self-rating scales commonly in use in The Netherlands. In addition the structure of EPDS was analyzed by various factor analyses to reveal some of its dimensional aspects. The Dutch version of EPDS was found to be a self-rating scale with good psychometric characteristics which measures what it claims to measure: the strength of depressive symptoms. With LISREL a 2-factor model could be distinguished which contained subscales reflecting depressive symptoms and cognitive anxiety.

Measuring depression in women around menopausal age: towards a validation of the Edinburgh Depression Scale.

BACKGROUND: The relationship between menopause and depression is still rather unclear. Studies using different methodology - especially those lacking a clear definition of depression - are hardly comparable. Since the Edinburgh Depression Scale (EDS) is not influenced by (menopause-related) somatic symptoms, the validity of the Dutch version of this instrument was investigated in a large community sample of menopausal women. METHODS: In 951 women, aged between 47 and 56 years, depressive symptomatology was measured using the EDS, together with a syndromal diagnosis of depression using Research Diagnostic Criteria. RESULTS: Twenty-two percent of the subjects had scores of 12 or higher on the EDS. With this cut-off point, depression (major or minor) was detected with a sensitivity of 66%, a specificity of 89%, and a positive predictive value (PPV) of 62%. A cut-off score of 15 or higher detected half of the women with major depression (sensitivity 73%, specificity 93%, PPV 53%). LIMITATIONS: Screening of depressive symptomatology at menopausal age in women of the community can only partly detect women with clinical depression. The relation between menopausal status and depression should preferentially be investigated using a longitudinal rather than a cross-sectional design. CONCLUSIONS: The EDS, which is easy to implement in both community and clinical settings (e.g., General Practice), might be used as an effective screening tool for detecting women at menopausal age who are at risk for depression, followed by clinical evaluation in those with high scores.

The effectiveness of Dry Bed Training for nocturnal enuresis in adults.

Nine enuretic adults were successfully treated by the Dry Bed Training in a fairly short time (means = 15 weeks) including the retraining period for 3 Ss who relapsed after the therapy. There were no differences between primary and secondary (nocturnal) enuretics. The few relapses were neutralized by a short retraining. The study shows that this minimal intervention treatment is effective and efficient.

Relapse rate and subsequent parental reaction after successful treatment of children suffering from nocturnal enuresis: a 2 1/2 year follow-up of bibliotherapy.

Results 2 1/2 years after an enuresis nocturna training are presented, including rate of success, percentage and duration of relapse for 113 children (mean age 11.6 year at the start of the training). The bibliotherapeutic treatment by parents did not require any intervention by a professional. Behaviour of parents in the event of a relapse differed between training conditions. Children in the Arousal condition recovered faster from a relapse, 90% of their parents used the Arousal training again at relapse or did not intervene at all and none of them consulted a professional. Clearly they had confidence in the method of Arousal training: combining the alarm device with reinforcement for correct behaviour at the time the alarm goes off. Parents in control conditions did not use the alarm device as often as the parents in the Arousal condition, but tried other means with less success, including consulting professionals.

Arousal training for children suffering from nocturnal enuresis: a 2 1/2 year follow-up.

Arousal Training is a fast, simple, and effective form of bibliotherapy for nocturnal enuresis with non-clinical children between 6 and 12 years of age. The parents act as therapists. They reward the operant behavior-pattern following the urine alarm. The success rate is 98% (N = 41), which is significantly high when compared to the control conditions (79%, N = 86). There was a response rate of 100% and no drop-out from therapy. All parents (N = 127) completed and returned the record. The results of a follow-up of this bibliotherapy (N = 113) 2 1/2 years later are presented. The success rate of Arousal Training was still significantly higher (92% continent) when compared to the urine device with specific instructions (77%) and urine alarm only (72%). Arousal Training is the treatment of choice for non-clinical enuretic children between 6 and 12 years of age.

Performance anxiety among professional musicians in symphonic orchestras: a self-report study.

155 of 650 professional musicians playing symphonic orchestras in The Netherlands completed a self-report questionnaire concerning performance anxiety. 91 of the 155 respondents reported experiencing or having experienced performance anxiety seriously enough to affect their professional or personal lives. There appeared to be no difference in prevalence between men and women. Substantial percentages of the anxious musicians reported considerable anticipation anxiety days (36%), weeks (10%), or even months (5%) prior to a performance. The results indicate that performance anxiety is a significant professional problem. It is suggested that teaching explicit coping strategies should be incorporated in the curricula of schools of music.

Ligand release-independent transactivation of epidermal growth factor receptor by transforming growth factor-beta involves multiple signaling pathways.

Many of the signaling responses induced by transforming growth factor-beta (TGF-beta) are mediated by Smad proteins, but there is evidence that it can also signal independently of Smads. Here, we provide evidence that multiple signal pathways induced by TGF-beta1-including Src family tyrosine kinases (SFKs), generation of reactive oxygen species (ROS), de novo protein synthesis and E-cadherin-dependent cell-cell interactions-transactivate the epidermal growth factor receptor (EGFR), which in turn regulates expression of c-Fos and c-Jun. Immunoprecipitation and immunofluorescence staining showed that EGFR was phosphorylated on tyrosine in response to TGF-beta1. EGFR transactivation required the activation of SFKs and the production of ROS via NADPH oxidase, but was not dependent on metalloproteases or the release of EGF-like ligands. In addition, the production of ROS was dependent on signaling by specific SFKs as well as de novo protein synthesis. Stable transfection of E-cadherin into MDA-MB-231 cells as well as E-cadherin-blocking assays revealed that E-cadherin-mediated cell-cell interactions were also essential for EGFR transactivation. Finally, EGFR transactivation was involved in the expression of c-Fos and c-Jun via the extracellular signal-regulated kinase signaling cascade. Taken together our data suggest that ligand release-independent transactivation of EGFR may diversify early TGF-beta signaling and represent a novel pathway leading to TGF-beta-mediated gene expression.

PTSD in persons with burns: an explorative study examining relationships with attributed responsibility, negative and positive emotional states.

A sample of 90 persons who had been hospitalized for severe burns were interviewed 1-4 years after the incident. Current DSM-IV post-traumatic stress disorder (PTSD) was assessed with the Composite International Diagnostic Interview. Perceived attributed responsibility and related positive and negative emotional states were examined using a semi-structured interview. Findings showed that PTSD was established in 8% of the participants and partial PTSD in 13%. In a homogeneity analysis (HOMALS), PTSD was associated with the attribution of responsibility for the incident to impersonal relationships and with a negative emotional state. The absence of (partial) PTSD was associated with the attribution of responsibility to close relationships, internal and circumstance-related attribution of responsibility and neutral or forgiving feelings. In logit analyses, both emotional state as well as attributed responsibility are significantly related to (partial) PTSD. However, the model including emotional state showed to have the best fit. Although further research is needed, these results may indicate that professionals working in burn care should consider the emotional state in relation to perceived attribution of responsibility when considering PTSD. Promoting forgiveness may be a beneficial strategy in dealing with post-traumatic stress reactions.

Predicting symptoms of depression from reports of early parenting: a one-year prospective study in a community sample.

The purpose of this study was to determine whether (reported) parental over involvement and lack of affection identify initially healthy subjects at risk for depression. One thousand subjects from the province of Utrecht, the Netherlands were randomly selected by using telephone addresses and asked to participate in a one-year prospective study on psychological risk factors of depression. From the 108 subjects that finally participated on both occasions, the reports of parental upbringing (Parental Bonding Instrument) of initially non-depressed subjects with a Zung Self-rating Depression Scale score below 49 points were used to predict new cases of depression one year later. Initially non-depressed subjects who reported maternal over involvement in the upper quartile of the distribution had an 8.5-fold increased risk (95% confidence interval 0.9 to 80.6) of becoming depressed one year later. Although initial reports of low paternal affection were positively associated with initial symptoms of depression, this characteristic failed to show predictive value. Parental upbringing deficiencies have frequently been shown in cross-sectional inpatient studies in which retrospective retrieval from memory because of depressive state characteristics may have caused negative colouring. Our results would suggest that maternal over involvement reported in the absence of a depressed mood still proves to be an important psychological risk factor in the aetiology of depression.

The validity of the Five-Minute Speech Sample as an index of Expressed Emotion in parents of eating disorder patients.

This article examines the concurrent validity of the Five-Minute Speech Sample (FMSS) as an index of Expressed Emotion in a Dutch sample of 84 parents of adolescents suffering from anorexia or bulimia nervosa. The Camberwell Family Interview (CFI), the criterion measure of EE, and the FMSS were conducted on the same day. The levels of Expressed Emotion in these families were low when compared with the EE ratings from the schizophrenia studies. The FMSS and CFI-EE ratings showed a limited degree of overlap. Whether the limited association between the two methods is due to the low levels of criticism in our sample, to cultural differences and/or to differences in the psychopathology under study remains unclear.

Expressed emotion and the prediction of outcome in adolescent eating disorders.

OBJECTIVE: This study examines whether parental Expressed Emotion (EE) ratings, based on the Camberwell Family Interview (CFI), are predictive of the course of illness in a sample of Dutch families with an adolescent eating disorder patient. Levels of EE at first assessment and at the termination of treatment are reported. METHOD: The study was designed as a prospective follow-up study and involved 49 adolescent eating disorder patients (DSM-III-R) and their parents. Patient and family assessments were conducted at intake (T1), at the termination of treatment (T2), and at follow-up (T3) 1 year later. The Morgan-Russell Outcome Assessment Schedule, which was adjusted to accommodate bulimics, yielded the average outcome score (AOS) which served as our outcome measure. RESULTS: The levels of parental EE at first assessment were low. During the treatment period the levels decreased further. We used a stepwise multiple regression analysis, with the parental EE variables as independent variables, to predict the AOS at T2 and T3. This way we showed that the mothers' Critical Comments (CC) rating explained 28 to 34% of the outcome variance. The mothers' CC rating was also the best predictor of outcome when compared to other possible predictor variables. DISCUSSION: The results underscore the importance of involving the family in the treatment of adolescent eating disorders. Specific attention should be given to the mother's thoughts, feelings, and behavior concerning her ill daughter. Helping the mother and daughter to differentiate and separate through a constructive noncritical approach to the presenting problems may be a crucial factor in breaking through the perpetuating cycle of criticism and illness.